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These are 4 medical innovations coming out of Houston institutions – InnovationMap

Posted: February 19, 2020 at 12:45 am

Houston home to one of the largest medical centers in the world isn't a stranger when it comes to medical innovations and breakthrough research discoveries.

In the latest roundup of research innovations, four Houston institutions are working on innovative and in some cases life-saving research projects.

If the germ,group A streptococcus, continues to grow resistant to antibiotics, it can have a profoundly negative affect on the millions who get the illness annually. Photo via houstonmethodist.org

Researchers at Houston Methodist have discovered some troubling information about the strains of group A streptococcus that cause strep throat and a flesh-eating disease are becoming more resistant to beta-lactams antibiotics like penicillin.

James M. Musser is the lead author of the study and chair of Methodist's Department of Pathology and Genomic Medicine. The study which received funding from grants from the Fondren Foundation, Houston Methodist Hospital and Houston Methodist Research Institute, and the National Institutes of Health appeared in the Jan. 29 issue of the Journal of Clinical Microbiology, according to a news release.

"If this germ becomes truly resistant to these antibiotics, it would have a very serious impact on millions of children around the world," Musser says in the release. "That is a very concerning but plausible notion based on our findings. Development of resistance to beta-lactam antibiotics would have a major public health impact globally."

Musser and his team found 7,025 group A streptococcus strains that have been recorded around the world over the past several decades. Of those strains, 2 percent had gene mutations that raised the alarm for the researchers and, upon investigation, Musser's team came to the conclusion that antibiotic treatments can eventually be less effective or even completely ineffective. This, Musser says, calls for an urgent need to develop a vaccine.

"We could be looking at a worldwide public health infectious disease problem," says Musser in the release. "When strep throat doesn't respond to frontline antibiotics such as penicillin, physicians must start prescribing second-line therapies, which may not be as effective against this organism."

University of Houston Professor Mehmet Orman is looking into cells that are able to persist and cause chronic illnesses. Photo via uh.edu

Mehmet Orman, assistant professor of chemical and biomolecular engineering at the University of Houston, is looking into a specific type of persister cells that have been found to be stubborn and drug-resistant.

The research, which is backed by a $1.9 million grant from the National Institute of Allergy and Infectious Diseases, could answer questions about chronic health issues like airway infections in cystic fibrosis patients, urinary tract infections, and tuberculosis, according to a news release.

"If we know how persister cells are formed, we can target their formation mechanisms to eliminate these dangerous cell types," says Orman in a news release.

Orman is looking into cells' self-digestion, or autophagy, process that is found to stimulate persister formation. Per the release, cells can survive periods of starvation by eating their own elements. Specifically, Orman will analyze self-digestion in E. coli.

"By integrating our expertise in bacterial cell biology with advanced current technologies, we aim to decipher the key components of this pathway to provide a clear and much-needed picture of bacterial self-digestion mechanisms," says Orman in the release.

Some patients are predisposed to kidney injury following surgery, this study found. Photo via bcm.edu

Scientists at Baylor College of Medicine are looking into the lead cause of kidney failure in patients who undergo surgery. Individuals who have heightened levels of suPAR protein soluble urokinase-type plasminogen activator receptor have a greater risk of this post-op complication, according to a news release.

"suPAR is a circulating protein that is released by inflammatory cells in the bone marrow and produced by a number of cell/organs in the body," says Dr. David Sheikh-Hamad, professor of medicine nephrology at Baylor College of Medicine and collaborating author of the study, in the release.

The study, which was published in The New England Journal of Medicine, conducted research on mice that were engineered to hive high suPAR levels in their blood. Compared to the control mice, the suPAR mice had more risk of kidney industry. These mice were given suPAR-blocking antibodies, which then helped reduce kidney injury.

"This protective strategy may be used in humans expressing high suPAR levels prior to contrast exposure, or surgery to decrease the likelihood of developing kidney failure," Sheikh-Hamad says in the release.

Christopher Fagundes of Rice University analyzed the emotions of 99 widows and widowers. Jeff Fitlow/Rice University

A new study done by researchers at Rice University finds that spouses that lose their husband or wife and try to suppress their grief are not doing themselves any favors. The study monitored 99 people who had recently lost a spouse, according to a news release.

"There has been work focused on the link between emotion regulation and health after romantic breakups, which shows that distracting oneself from thoughts of the loss may be helpful," says Christopher Fagundes, an associate professor of psychology and the principal investigator, in a news release. "However, the death of a spouse is a very different experience because neither person initiated the separation or can attempt to repair the relationship."

The study included asking participants to respond to how they felt about certain coping strategies, as well as blood tests to measure cytokines levels an inflammatory marker.

"Bodily inflammation is linked to a host of negative health conditions, including serious cardiovascular issues like stroke and heart attack," Fagundes says in the release.

The research, which was funded by a grant from the National Heart, Lung, and Blood Institute, found that the participants who avoided their emotions suffered more of this bodily inflammation.

"The research also suggests that not all coping strategies are created equal, and that some strategies can backfire and have harmful effects, especially in populations experiencing particularly intense emotions in the face of significant life stressors, such as losing a loved one," adss Richard Lopez, an assistant professor of psychology at Bard College and lead author of the study, in the release.

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Alternative Splicing Identified as a Potential Driver of Aggressive Cancers – Clinical OMICs News

Posted: February 19, 2020 at 12:45 am

Researchers from Childrens Hospital of Philadelphia (CHOP) have led a multi-institutional group to study the link between a strong cancer driver gene that impacts changes in proteins related to alternative splicing regulation. The scientists developed new computational tools and biological model systems for the study, led by Yi Xing, Ph.D., at CHOP and Owen Witte, M.D., at the University of California, Los Angeles (UCLA).

Alternative splicing is the process in which exons and introns are separated in a pre-mRNA strand, and various combinations of exons in the mRNA can be used to translate into proteins.Through this mechanism, a single gene can code for multiple (usually closely related) proteins.

Alternative splicing is an essential process, and it is the RNA that is cut, or spliced, before being translated into proteins, meaning regulation happens at the transcription level. Cancer cells often take advantage of this process to produce proteins that promote growth and survival, allowing them to replicate uncontrollably and metastasize. This happens in many cancers, including prostate cancer, which is associated with shifts in splicing patterns. Yet scientists do not fully understand the process that leads to this change.

Our study provides insight into the relationship between an important cancer driver genes and alternative splicing changes that could be used to guide the development of splicing-targeted cancer therapy, said Xing, director of the Center for Computational and Genomic Medicine at CHOP and senior author of the study.

To better understand the causes and consequences of alternative splicing changes during cancer progression, the team examined RNA sequences from nearly 900 prostate tissue samples, ranging from healthy prostate tissue to localized or aggressive metastatic tumor tissue. To efficiently analyze such a large sequencing dataset, the team created a computational program called rMATS-turbo. This program allowed the researchers to identify more than 13,000 alternative splicing events that occurred across these 900 prostate samples.

The collaborative effort involved researchers at CHOP, UCLA, and the Roswell Park Comprehensive Cancer Center. John Phillips, M.D., Ph.D., a researcher at UCLA, and Yang Pan, a visiting scholar at CHOP and graduate student at UCLA, were first authors of the study.

After the team identified alternative splicing events and rate of occurrence, they developed an analytic tool, dubbed PEGASAS (Pathway Enrichment-Guided Activity Study of Alternative Splicing), to identify which splicing patterns led to the creation of proteins that may help drive cancer genes and pathways. They were searching for alternative splicing patterns that correlated to cancer development.

The scientists found that Myc, a gene normally involved in cell functions but amplified in many cancers, was linked to alternative splicing changes in genes that themselves regulate alternative splicing. Using human prostate cells that were engineered to turn on or off Myc activity, researchers further confirmed that these alternative splicing changes were indeed driven by Myc.

The team of researchers then applied the same PEGASAS strategy to breast cancer and lung cancer datasets and found the same association between Myc activity and alternative splicing, suggesting Myc activation and thus disruptions in splicing occur in many cancer types.

Of course, the MYC family of oncogenes is known to be deregulated in over half of all known human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism,meaning that it may be possible that alternative splicing is just one downstream effect this gene has during the cancer development process.

The successful application of PEGASAS to prostate, breast, and lung cancer datasets suggests that this strategy could be useful in analyzing pathway-driven alternative splicing in many cancer types, said Xing. Given the involvement of oncogenic pathways such as the Myc pathway in pediatric cancers, these tools could reveal pathways and targets for treating pediatric cancers as well.

While this research is in its early stages, linking protein changes to cancer development is an important step in understanding cancer development. If individual spicing patterns for particular proteins can be identified as cancer causing, it would open the door for precision medicine to step in and block those particular proteins from being translated.

It would be of great interest to see if alternative splicing was involved in cancer types that did not involve Myc, and if alternative splicing could be linked to cancers that involved different genetic mutation pathways.

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Bile duct cancer treatment potential boost from tailored medication – study – University of Birmingham

Posted: February 19, 2020 at 12:45 am

Treatment of patients suffering from bile duct cancer could be improved by tailoring medication to the levels of a key protein in people with the disease, according to new research.

Cholangiocarcinoma (CCA) is a deadly disease with few treatments, but researchers in the UK and Thailand have discovered that the PRH/HHEX protein is a key driver in the disease, with increased levels affecting the response of cancer cells to therapeutic drugs.

Formation of CCA is driven by alterations in the levels of the PRH protein which controls genes and signaling pathways in the body - a discovery which could allow doctors to use specific drugs to treat the cancer.

Researchers from the Universities of Birmingham and Nottingham worked with partners at the Chulabhorn Research Institute, in Bangkok. The study, funded by the Medical Research Council (Newton Fund) and Thailand Research Fund, is published in Cancer Research and featured on front cover of Cancer Research 15 February 2020 issue.

Dr Padma Sheela Jayaraman, from the Institute of Cancer and Genomic Sciences at the University of Birmingham, commented: "Clinical efficacy of chemotherapeutic strategies is likely to depend on PRH expression level. Tailoring patient medication according to the individual level of PRH expression could improve clinical usefulness of several compounds, recently suggested as potential novel treatments for bile duct cancer."

Aberrant Notch and Wnt signalling are known drivers of CCA, but the underlying factors controlling these pathways were not previously known.

The researchers found that hyper-activation of Notch and Wnt signalling is connected to dysregulation of PRH. Moreover, they suggest new therapeutic options based on the dependence of specific Wnt, Notch, and CDK4/6 inhibitors on PRH activity.

They demonstrate that expression of PPH is elevated in cases of CCA and that reduction in PRH levels reduced CCA tumour growth in a model of cancer. They showed that high PRH expression in primary human biliary epithelial cells isolated from human liver, by Dr Simon Afford from the University of Birmingham's Centre for Liver and Gastrointestinal Research, tended to increase cancer cell properties such as invasion and anchorage-independent growth.

Professor Kevin Gaston, from the University of Nottingham School of Medicine and Biodiscovery Institute, commented: "We are excited by the outcomes of this international collaborative study and we are working towards translating these findings into new ways of treating individual patients in the UK and in Thailand, where there is a particularly high incidence of CCA."

For more information, interviews and an embargoed copy of the research paper, please contact Tony Moran, International Communications Manager, University of Birmingham on +44 (0)121 414 8254 or +44 (0)7827 832 312. For out-of-hours enquiries, please call +44 (0)7789 921 165.

The University of Birmingham is ranked amongst the world's top 100 institutions, its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from over 150 countries.

'A runaway PRH/HHEX-Notch3 positive feedback loop drives cholangiocarcinoma and determines response to CDK4/6 inhibition' - Philip Kitchen, Ka Ying Lee, Danielle Clark, Nikki Lau, Jomnarong Lertsuwan, Anyaporn Sawasdichai, Jutamaad Satayavivad, Sebastian Oltean, Simon Afford, Kevin Gaston and Padma-Sheela Jayaraman is published in Cancer Research and featured on the front cover of the 15 February 2020 issue.

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ALK Rearrangement Adenocarcinoma with Histological Transformation to S | OTT – Dove Medical Press

Posted: February 19, 2020 at 12:45 am

Taisuke Kaiho,1 Takahiro Nakajima,1 Shunichiro Iwasawa,2 Yoko Yonemori,3 Ichiro Yoshino1

1Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan; 2Department of Respirology, Chiba University Graduate School of Medicine, Chiba, Japan; 3Department of Pathology, Chiba Rosai Hospital, Chiba, Japan

Correspondence: Takahiro NakajimaDepartment of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, JapanTel +81-43-222-7171Fax +81-43-226-2172Email takahiro_nakajima@med.miyazaki-u.ac.jp

Abstract: Specific tyrosine-kinase inhibitors (TKIs) are widely used for the treatment of non-small-cell lung cancers with anaplastic lymphoma kinase (ALK) translocations. However, most treated patients eventually develop resistance to the TKIs. The histological transformation into small cell carcinoma is well known to be the underlying mechanism for acquired resistance; however, transformation to squamous cell carcinoma is extremely rare. We, herein, report a case of ALK rearrangement-positive adenocarcinoma that transformed to squamous cell carcinoma after administration of alectinib, and was found to be resistant to ceritinib.

Keywords: lung adenocarcinoma, anaplastic lymphoma kinase, transformation, squamous cell carcinoma, acquired resistance

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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High-throughput Technologies in Drug Discovery – Technology Networks

Posted: February 19, 2020 at 12:45 am

Bringing new medicines to patients struggling with serious illness is the driving force behind drug discovery and development. Originating as small molecules, drugs have shifted to large molecule therapies and will continue to shift as precision medicine is adopted. In spite of these different types of drugs, the development time to create them has not changed dramatically. It still takes 10 to 15 years to bring a drug to market. For this reason, there is tremendous interest when it comes to finding ways to develop drugs with higher throughput methods. This article highlights advances in three technology areas that show great promise to speed the drug discovery and development process.Automation and roboticsThe need for automation and robotics is not a new topic in drug discovery but an area where great progress has been and continues to be made. Automation is essential to implementing high-throughput strategies. What started out as a solution to achieve higher throughput has extra benefits. An automated process provides better data quality due to process consistency. Human error is minimized, and the presence of an audit trail allows traceability if questions arise. Automation also provides walk away freedom for the scientist to pursue other tasks.

To witness an automated set up, one may find that each automation step may not be fast in and of itself. But consider the shift away from an 8-hour employee workday to one of continuous 24-hour operation. Screening projects are now reduced by at least a factor of 3, thus yielding higher throughput.

Automation can be categorized into three general modes defined as (1) batch, (2) semi-automated, and (3) integrated. The three modes range from limited to extensive on key automation criteria which include things like flexibility, walk away capabilities, number and complexity of tasks. Batch mode, for example still requires a scientist to load stacks of plates that then are subjected to a limited step in the process. Integrated automation, the most sophisticated, is capable of carrying out multiple scheduled steps facilitated by a robotic mover. This allows unmanned operation for extended periods providing walk away or overnight convenience.1An important consideration in any automated solution is the skill requirement of the operator. More sophisticated systems will require automation programming skills often leveraging automation engineers. Specialized training from the equipment vendor may also be required. Batch automation can often be accomplished with little specialized training. Compared to ten years ago, automation today has evolved and become more democratized. This continued trend will reduce the need for specialized training in the future with more turn-key and intuitive solutions becoming commercially available.

David Ebner, Principal investigator at the Target Discovery Institute in Oxford, UK explains: There are two key limiting factors for any group trying to do high-throughput screening today. The first is the expertise to translate a benchtop assay to a high-throughput platform and the second factor is the expense. Centralized core facilities are one way to address the expense factor. And as automation becomes more turn-key, the need for specialized engineers is reduced, allowing future resources to be more research scientist driven.

The discovery and development of small molecules and antibodies targeting T cell function, as well as T cell-based cell therapies and cell manufacturing, require assays to rapidly and reliably profile T cell activation and cell health. In this app note, discover how phenotypic screening addresses these needs, using a single assay to provide rapid, optimized monitoring of cell proliferation, activation markers and cytokines.

Microfluidic technology, a more extreme form of miniaturization, addresses some of these known fluid handling challenges.4 Microfluidic chips provide the benefits of reduced volumes while replacing liquid handling mechanics with channels connected to liquid reservoirs. In some cases, the device has integrated tools such as electrodes built-in and can combine multiple operational steps. 5Microfluidic devices are also able to isolate single cells, which can be further cultured on the chip. This ability removes cellular heterogeneity on cancer cell populations as an example. Traditional drug screening methods see response information from an average of all cells. The microfluidic solution allows analysis of a single cell's antidrug response.4 In addition to this cell-on-chip model, recent advances have led to tissue-on-chip and organ-on-chip models which are still early in development. These kind of chip models may someday provide a powerful alternative to animal models.6 Because they are early in development, they are not high- throughput solutions today. But they show great promise to speed determination of drug activity, optimal combinatorial drug screening and toxicity testing in the future.4Artificial intelligenceApplied to drug discovery, artificial intelligence (AI) has been used in medicinal chemistry for designing compounds since the 1960s. 7 Machine-learning tools like quantitative structure-activity relationship (QSAR) modeling have identified potential target molecules from millions of candidate compounds. 8 Today, AI has expanded its application in drug discovery to a range of tasks from robotics control to image analysis and logistics. AI has also been applied throughout the drug discovery process from target selection, hit identification, lead optimization through to preclinical studies and clinical trials. 7, 8Dr Mohammad HamediRad and colleagues at the University of Illinois explain that with new uses of AI, "the role of researcher changes from drivers of the experiments to supervisors of the system." AI, integrated with robotic systems enables automation of the design, build, test, and learn (DBTL) cycle. This results in a platform that designs experiments, executes them, analyzes the data then optimizes and executes subsequent experiments iteratively. This closed loop discovery reduces the total number of experiments and generates the best possible optimization. The concept was demonstrated by HamediRad and colleagues in 2019. Their fully-automated platform evaluated less than 1% of possible variants and outperformed traditional screening methods by 77%.9AI platforms can cut down the development time from lead molecule to a candidate by more than half. AI predicted molecules are more likely to be correct and allow a focused effort. Time isnt wasted testing irrelevant molecules which would have been worked on otherwise and make up 90% of the molecules tested by traditional methods.10 Currently, AI can help find novel compounds which are more potent and selective using high quality screening data sets much faster and at less expense than screening alone, explains Ebner.

Personalized or precision medicine is another area where AI plays an important role. Precision medicines are a growing proportion of drugs in the industry pipeline. 11 Extensive collections of human samples (diseased and healthy) are required for biomarker identification in developing a personalized medicine. 12 Typically, all samples are sequenced using next-generation sequencing which generates massive amounts of data. AI methods of deep-learning make analysis of these big data sets possible. 8Automation Journey Guide: How To Automate Simple to Complex Workflows To Achieve Results Beyond High-throughput

Laboratory automation is playing a key role in advancing scientific research, from pharmaceutical development to diagnostics. Whether it is to automate a simple or sophisticated workflow, automation is now used in labs throughout the world to increase their capacity and throughput. In this eBook, discover a detailed guide to introducing automation to your lab.

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A Secret Report Revealed How Prison Guards Allegedly Beat, Hog-Tied, And Tried To Conceal Abuse Of An Inmate – BuzzFeed News

Posted: February 19, 2020 at 12:45 am

Handout

Billy Smith and his mother, Teresa Smith (left); Smith's graduation photo.

This article was published in collaboration with Injustice Watch, a nonprofit newsroom focused on exposing institutional failures that obstruct justice and equality.

MONTGOMERY An Alabama prisoner died weeks after he was allegedly beaten by a fellow inmate, beaten again and hog-tied by prison guards, and then denied treatment by a nurse, according to a secret Alabama Department of Corrections report obtained by Injustice Watch.

The report contains shocking details about the death of Billy Smith, including apparent efforts to conceal the timeline of events and obscure the roles that correctional employees played in his fatal ordeal.

Smith, 35, was found dazed and injured on the floor of a bathroom at Elmore Correctional Facility in November 2017 after another man allegedly punched him in the head and knocked him out over a bungled drug deal.

Inmates took Smith, bloodied, to the shift command office, where witnesses said he complained about head pain and refused to wait outside. Officers then beat Smith, hog-tied him, and left him strapped to a gurney.

Smith lay untreated for at least an hour, witnesses said in the report, bleeding heavily from his nose and pleading for help.

Officers then took him to a nearby prison medical facility, where a nurse refused him treatment. When authorities returned with Smith, he was unconscious and trembling.

Prison officials then sent Smith back to the medical facility, and paramedics took him to a hospital. Smith, who suffered a fractured skull and brain bleeding, never woke up again. He died 26 days later from blunt force head trauma.

Smiths mother, Teresa Smith, said the Alabama Department of Corrections never reached out with condolences or an explanation. Smith, who left behind three children, was serving time for a 2006 murder.

For him to have to die like that he got the death penalty in my view, Teresa Smith said in an interview with Injustice Watch. People say he deserved what he got, but nobody deserves to suffer like that. I know that inmates are prisoners, and maybe they are there for a reason, but they're not animals; these are people's sons, brothers, and daddies.

The details of how guards allegedly left Smith without prompt care for his wounds and then inflicted more injuries were included in the confidential investigative report that the Alabama Department of Corrections has kept secret from the public. In the report, inmates contradicted the explanations correctional staff gave investigators. Some prison supervisors first denied seeing Smith hog-tied, but later revised their statements or were otherwise called into question by video described in the report. An office log was found apparently altered, with notes about Smith missing and a dubious signature. One sergeant failed a polygraph exam, and an assistant warden edited her time card without explanation, according to the report.

Injustice Watch emailed the Alabama Department of Corrections with a long list of questions and sought interviews about what investigators found. Officials responded with a statement confirming that they had probed the circumstances around Smiths death and forwarded findings to prosecutors, but declined to say much more, out of respect for the legal process.

Bryan Blount, who was serving time at Elmore for a 2002 murder, is scheduled to go on trial for manslaughter next month for allegedly causing Smiths death. So, too, is former correctional officer Jeremy Singleton, who prosecutors say struck Smith multiple times on his head and failed to seek timely medical attention for the inmate.

Mickey McDermott, Singletons lawyer, said his client is innocent. Blounts attorney didnt return calls for comment. Neither did the state medical examiner who investigators said concluded that Blount was responsible for Smiths death. Injustice Watch also reached out to the other officers accused of abusing Smith, the nurse who denied his care, and prison supervisors mentioned in the report. All either failed to respond to requests or refused to answer questions about what state investigators found.

The Shift Commanders Office

Late in the afternoon of Nov. 13, 2017, prisoners found Smith with a bruised forehead and a bloody nose in a prison dormitory. Two officers were watching the dorm, according to the report, which houses nearly 200 inmates.

Prisoners told investigators that Blount punched Smith in the head about 5:30 p.m., knocking him to the concrete floor. The fight was over money Blount accused Smith of shorting a package of synthetic marijuana. Prison officials alleged that Smith smuggled drugs for Blount from a nearby trade school where Smith attended classes. Smith, of Arab, Alabama, had struggled with addiction and crime since his teen years, his mother said.

Former Elmore correctional officer Joel McClease told Injustice Watch that an inmate brought him to the bathroom, where he found Smith lying on the floor by a toilet. Other prisoners told him Smith was intoxicated. McClease remembers helping Smith to a shower, saying he was conscious but unsteady on his feet. McClease said guards were typically advised to send injured or sick inmates to the shift office so that supervisors could then take them to a nearby prison health facility where nurses could evaluate their condition and fill out a body chart.

The bunks at Elmore Correctional Facility.

McClease said he radioed supervisors and requested that an ambulance unit of inmates come with a stretcher and transport Smith to the front shift command office.

According to the report, one of the inmates in the ambulance unit told investigators he remembered finding Smith lying on the floor, possibly intoxicated, wearing only boxers and a sweatshirt after his shower. He had a cut atop his head and a bloody nose.

Smith stood and was helped into the gurney. He was taken to a grassy area outside the shift commanders office, where it was cool and raining. About an hour had passed since the fight.

Nurse Tara Parker was in the office passing out medicine to a long line of inmates. Singleton had just arrived to work an overtime shift as a transport agent, moving inmates from prison to prison. At least two supervisors, Sgt. Jonathan Richardson and shift commander Lt. Kenny Waver, were in the office as well. Waver, according to the report, said he threatened Smith with a can of mace when Smith first arrived on the gurney, because he refused to sit down. But both shift leaders denied hitting Smith or seeing anyone abuse him, and both didnt return calls and letters seeking comment.

Smith continued to complain that he was cold and that his head was hurting badly. According to what several inmates told investigators, Smith defied correctional officers who told him to stay out of the office for fear he would track blood inside.

As the situation escalated, Singleton allegedly smacked Smith hard in his face and head, punched him twice in the ribs, and swept his feet from under him, causing him to fall on his side, three prisoners who helped guards transport Smith said in the report. McClease told Injustice Watch that he left his post to smoke a cigarette, looked down toward the shift office and saw Singleton hit Smith.

Singleton was coming out of the door, and Billy was standing on the wall right next to the door, and Singleton turned around and punched him, he said. And everybody who was in the pill call line scattered.

Several prisoners also accused other officers in the report of attacking Smith. Officer Ramus Johnson allegedly "grabbed inmate Smith by the shirt with his left hand and slapped him twice with his right hand and pushed him to the ground, according to one account. Another prisoner claimed to have seen Officer Walter Green punch Smith in the ribs after putting on gloves with hard plastic knuckles. Neither of the officers responded to repeated requests for comment.

At some point, witnesses alleged, Singleton punched Smith in the face and then hogtied him with help from other officers. They cuffed his hands behind him, shackled his feet, and then connected the cuffs to the shackles. Many law enforcement agencies have banned this sort of dangerous restraint method. Some critics liken it to torture.

Smith was laid on his stomach on the gurney, strapped in, and left behind the office beyond the view of cameras, yelling for help for at least an hour or more, according to the report. After he began to vomit, Waver ordered Singleton and rookie officer Ell White to take Smith to the health care unit down the road at Staton Correctional Facility. White, whose personnel file says he is a motor transport operator for the Alabama National Guard, didnt return requests for comment.

Inmate runners said the officers unstrapped Smith and that he walked to a prison transport van near the back gate. Video footage showed the van leaving the prison about 9 p.m. Smith entered Staton under his own power, Singleton and White said. But he didnt leave that way, according to the report.

Denied Care

Parker, the nurse, told investigators that she left the shift office at Elmore Correctional Facility and returned to Staton to find the officers in a hallway with Smith. Parker said she told the officers that she needed a few minutes to get settled, but would return. The officers placed Smith in a holding cell to wait.

The officers told investigators they saw Smith sitting on a bench with his eyes closed, and that he eventually slid off and began kicking, hitting his head on the floor, and grabbing at Singletons legs. They said they didnt hit Smith or let him fall.

White said Smith collapsed when officers tried to get him to stand up. Smith became unresponsive, so White rapped him lightly on the back of his neck to wake him. It was nothing ruthless, he said. White declined to take a polygraph about that account.

In a second interview, White said that he picked up a water cooler inside the cell and began pouring water over Smith to wake him up. He also said Singleton poured water and ice over Smith, but Singleton denied it. Nurses later discovered the sound of water in Smiths lungs, according to the report.

When Parker got to the cell, she said there was blood smeared on the walls, and that she found Smith rolling around on the floor, thrashing and yelling. Parker remembered the officers saying that Smith was wigging out on drugs, investigators said. In Parkers statement, she admitted that she made two big mistakes: The nurse did not complete a body chart on Smith, and she ultimately refused to treat him, she said, because he was acting erratically.

Parker initially told investigators she didnt see water on the ground in Smiths cell and didnt see anybody pour water on him. More than two months later, Parker gave a second statement, telling investigators that she did see White pour water over Smith in the holding cell.

The bathroom at Elmore Correctional Facility.

Once Parker refused to treat Smith, the officers said they loaded Smith into a wheelchair and rolled him to the van. Singleton said that the officers buckled Smith into the van, but that he unbuckled himself and tore at his clothing. But White, in his second interview, had a different story than Singleton: Smith was not moving when they got to the van, and the officers didnt buckle him into his seat.

The van was captured on camera returning to Elmore just after 10 p.m., about an hour after Smith was taken to Staton. At least two inmate runners helped unload Smith. They saw him lying on his left side, unresponsive, stuck between two benches, with his shirt over his head, his pants around his ankles, and his boxers down to his thighs, according to the report. One of the runners said that he pulled a trash bag filled with ice from between Smith's chest and one of the seats.

The inmates who transported Smith, as well as a supervisor who saw him after he returned to Elmore, offered the same account: Smith was wet, shaking uncontrollably, and making a strange snoring noise. Oh my god, Waver exclaimed when Smith was rolled back to the shift office, according to one inmate runners account. Supervisors then ordered him taken back to Staton.

Parker and one of the inmate runners said that Smith returned to Staton with several marks on his body that were not there before. Parker told investigators it appeared Smith had been dragged. After nurses evaluated his condition, they gave him medicine meant to treat drug overdoses, but it had no effect, according to the report. After that, authorities took Smith to Jackson Hospital, in Montgomery, but the report doesnt say when.

There are discrepancies in different witness accounts. Some inmates, including retired officer Joel McClease, said that they saw Smith walking on his own closer to 10 p.m.

One of the prisoners who helped transport Smith initially declined to talk to investigators until he was transferred to another prison, 25 miles away. There, he gave investigators a statement largely supporting the descriptions of how Smith was mistreated. He later told investigators that Singleton unexpectedly visited him, saying, I suppose I know why you are up here."

The prisoner said Singleton confided that "they are trying to pin that inmate's death on me, and then told him to stay strong.

The prisoner told investigators that he took the statement to mean he should stay quiet about what happened to Smith, according to the report.

John Crow, who was the warden at Staton during Smiths incident but has since moved on to another facility, didnt return calls for comment. And nurse Parker, contacted in February by Injustice Watch, refused to answer questions about what happened at the shift office or the medical facility in 2017, when Smith suffered fatal injuries while she was on duty.

"Please respect the fact that I do not want to talk about this case, she said. I do not want to be bothered anymore about the situation.

Exceptionally Cleared

The Alabama Department of Corrections Investigations and Intelligence Division began looking into Smiths injuries on Nov. 14, 2017, the day after he arrived at the hospital.

Investigator William D. Favor and a partner, T.A. Wallace, found Smith unconscious, visibly battered, and recovering from an emergency brain surgery when they arrived at the hospital. A nurse told the investigators that Smith had a fractured skull on the left temporal area of his head and a swollen brain that had shifted to the right. Favor wrote in his report that Smith was brought to the hospital due to a possible drug overdose.

The investigators reviewed his body and observed several cuts to the top of his head, abrasions and bruising on both legs, hips, shoulders, however; he did not appear to have any defensive marks or bruising on his arms nor did he have any cuts to his knuckles and hand that would indicate hitting any object with his fist.

ThenElmore Correctional Facility warden Joseph Headley, who didnt return Injustice Watchs requests for comment, was among the first people Favor interviewed. Headley, now the warden at Staton Correctional Facility, never indicated that guards or nurses had mishandled Smith, according to investigators. Instead, he helped connect investigators with alleged witnesses to Smith and Blount's dormitory fight.

When investigators later approached prison leadership with harder questions about what had happened to Smith under their watch, and asked whether officers had abused Smith, leaders responded with apparent defensiveness, deception, and a lack of cooperation, the investigators report shows.

Assistant Warden Gwendolyn Babers, who refused to be interviewed for this story, denied ever seeing an inmate abused, according to the report. A prisoner, however, alleged that Babers had exited out the front side door in view of the shift office, and spoke to Waver briefly while Smith was hog-tied. Investigators couldnt confirm that inmates account. And Babers time card showed that she clocked out about 40 minutes before Smith was brought to the shift office, according to the report. However, investigators noted that Babers time card was edited on the day Smith was hurt, and that the reason for the editing is unknown.

Waver denied that any officers under his command struck Smith and denied seeing Smith hog-tied on the gurney, though in a later interview he acknowledged seeing Smith handcuffed and shackled on the gurney outside the office for an hour or more.

Richardson denied seeing any officer strike Smith and said he could not confirm if he was hog-tied. The corrections sergeant said he had only been outside the office once during Smiths ordeal when other witnesses said he was being beaten but video later showed he had been outside at least six times, according to investigators.

Investigators also found that the original copy of a shift office log was missing notes about Smiths first trip to Staton that a clerk remembered entering, and it lacked a required signature from a supervisor. A copy of the unsigned, incomplete log was found on a clipboard in the womens bathroom. The purported original was later found in a locked file cabinet bearing Richardsons signature.

Richardson denied knowing whether anyone had changed the shift log and insisted that he had signed the log. He failed a polygraph exam when agents asked him if he had seen Smith hog-tied, if he had signed the shift log after it had been altered, and if he knew who had made the changes, the report shows.

A state autopsy concluded Smith had died of blunt force trauma. After hearing investigators describe the details of Smith's fight with Blount and witness statements about Smith's contact with officers, a medical examiner with the Alabama Department of Forensic Sciences attributed Smith's fatal injuries to his fight with Blount.

In February 2019, one of the investigators referred a manslaughter charge against Blount to the Elmore County District Attorneys Office.

Investigators declared the Smith probe exceptionally cleared and closed it in October 2018, due to the case against the inmate. But in July 2019, the grand jury returned indictments against both Blount and Singleton, who had been promoted to sergeant a year prior.

Prison officials put Singleton on mandatory leave after learning of the indictment, and he resigned about a week later, in August 2019, according to a statement from the Department of Corrections.

Both Singleton and Blount are scheduled to begin trial on March 23.

McDermott, Singletons lawyer, said the state of Alabama cant have it both ways by charging both men with manslaughter even though a state autopsy concluded Blount was at fault.

He accused inmates of making false statements, blasted corrections staff at Elmore for allegedly scapegoating Singleton while other officers, supervisors, and nurses get off the hook in criminal and civil lawsuits.

Mr. Singleton has been sued civilly, hes been charged criminally, yet if you read the report, the person who denied medical treatment to Mr. Smith was a nurse, McDermott said. The nurse has not been charged, she has not been sued, but clearly she refused medical treatment to this inmate, and Im sorry, but if you look at it, it looks like her delay contributed to this mans death.

Smiths mother, Teresa Smith, also rejects the notion that only Blount and Singleton are responsible. That is one reason why her family filed a civil lawsuit against Singleton, Warden Headley, who transferred to Staton last year, Waver, state prison chief Jeff Dunn, and former associate commissioner Grantt Culliver, who retired in 2018 amid a sexual misconduct scandal.

She hopes that the story of how her son died can help spur greater accountability at Elmore Correctional Facility and other Alabama prisons, and urge consequences higher up the organizational chart when corrections employees mistreat inmates.

I want to save another mama, or another child, from having to feel pain like this, she said. I don't really blame the prisoner, because I don't think he killed my son. I know that the guards did it, and it wasn't just one person involved."

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Amish kids were dying mysteriously. Mayo scientists solved it. But can they treat it? – Minnesota Public Radio News

Posted: February 19, 2020 at 12:45 am

In 2004, Dr. Michael Ackerman got an unexpected phone call.

On the other end of the line was a medical examiner in Kentucky who had recently performed a befuddling autopsy on a 12-year-old Amish girl.

He was perplexed why this seemingly healthy Amish child died suddenly during play, said Ackerman, a genetic cardiologist at Mayo Clinic who studies why some young people die unexpectedly. And he says, I have DNA for you.

Ackerman, who also leads Mayos Windland Smith Rice Sudden Death Genomics Laboratory, pioneered a postmortem test to detect genetic causes behind sudden death. The medical examiner in Kentucky had heard about his work.

That phone call would ignite more than a decade of genetic sleuthing across multiple states to understand why a healthy Amish child had died without an obvious explanation. The mystery of her death and later, the deaths of more than a dozen other Amish children would vex researchers and clinicians for years, until Ackerman and his colleagues finally made a breakthrough in their Mayo lab.

Those findings were recently published in the JAMA Cardiology medical journal. Now, those same researchers are working to find a treatment.

Not long after the medical examiners call in 2004, Ackerman and his team were just beginning their research into the girls DNA when tragedy struck again. Four months after losing their daughter, the family lost her 10-year-old sister under similar circumstances suddenly, while she was outside playing.

Ackerman said his research team had a hunch the siblings deaths involved a gene called RYR2. When there's a single error on the gene, it causes an irregular heart rhythm that often reveals itself in the form of fainting spells while exercising. It can be fatal.

But that was more than 15 years ago, and medical research tools hadnt quite caught up to the teams needs.

Back then, it was painfully slow. It sort of was one gene at a time, Ackerman said.

After extensive testing of the girls' DNA, the Mayo researchers still had no answers.

We basically had a project that was stalled and would stay stalled until we would have evolution of technology, Ackerman said.

Over the next decade, 16 more Amish children died while exercising, without warning. The same family that lost their daughters in 2004 lost two more children under similar circumstances. Amish children in other states died, too.

While Mayos research languished, more than a thousand miles away, doctors at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., encountered a similarly tragic story.

In 2005, a young, apparently healthy Amish child was playing and died suddenly. The autopsy revealed no obvious cause. Several years later, the girls sister experienced cardiac arrest but survived and she is still living, 15 years later.

This started a trend, essentially, in their family, said Kristi Fitzgerald, a genetic counselor at Nemours and an author of the JAMA paper. Its not just a fluke chance, a terrible, tragic event. Now with two girls in one family, the presumption was that this probably was a genetic cause, something to do with a genetic arrhythmia.

But just as in Ackermans lab in Rochester, Minn., genetic testing at Nemours turned up nothing.

Over the years, Nemours staff collaborated with Mayo staff, and in the process learned that the sisters who had died in Kentucky were from the same extended family as the child who had died in Delaware.

Researchers also identified additional relatives in Iowa who have the same genetic defect. To date, no members of Amish communities in Minnesota appear to have the condition.

Clinicians at Mayo and elsewhere are fiercely protective of the families affected, and declined to identify them to maintain their privacy.

In Rochester, Ackerman and his staff continued to collect DNA samples from the children who died in this perplexing way, hoping someday to figure out the cause of their death.

They just needed the technology to catch up. In 2016, it started to.

Ackerman said new testing techniques revealed that the sudden deaths weren't caused by just one error on the RYR2 gene they were caused by 300,000 of them.

What's more, the risk of sudden death came only when the children inherited that faulty gene from both parents.

"We basically did genomic triangulation and figured that all of these sudden deaths and all of these different Amish communities were happening for the exact same reason: a double whammy, a double hit of this exact same duplication, Ackerman said.

Nemours pediatrician Matthew Demczko has made a career working with Amish children who live with an array of genetic abnormalities.

He said the genetic heart defect detected by the Mayo team is likely unique to the Amish community. Thats because researchers think people with the defect are all connected to a small number of people who established a particular Amish community from which the children affected were all descended. Those people are what Demczko calls "founder individuals."

Their genetic information has now become sort of the genetic thumbprint of the entire community, he said.

Demczko said Amish communities tend to be small and insular, and members of the community typically marry and have children with people who are also Amish.

That factor on top of the idea that from a cultural perspective, very few individuals come into the Amish community, there's really no introduction of new genetic material, he said.

Beating heart cells engineered from blood donated by two people living with a condition that has caused the sudden deaths of Amish children are shown on a microscope screen inside of the Mayo Clinic's Windland Smith Rice Sudden Death Genomics Laboratory.

Evan Frost | MPR News

Fitzgerald, Demczkos colleague, is on the front lines of screening members of Amish communities in their region for the defect. She said that Nemours positive reputation in nearby Amish communities helps in her work.

Word of mouth is important, she said. I think that's a great source of referral, to have a patient to say, We had a good experience. This went well.

Fitzgerald said her Amish patients ask the same questions about genetic testing as other families do: What will the test tell them? Why is the test important? What will they do with the information if they test positive?

And she said it's a misconception that Amish people shun medicine.

The families shes worked with, she said, have been open to testing and treatment.

"Parents want what's best for their child. It's about building a relationship, you know, with the family, she said. Most are not at all skeptical."

Fitzgerald said that some parents whose children have tested positive for the condition have opted to get an implantable defibrillator, which is the only available treatment.

But many Amish families dont carry health insurance, so that solution is not only invasive, but can be prohibitively expensive.

Back at Mayo, researcher Dave Tester is trying to better understand the genetic defect he helped discover. Now that theyve pinpointed the cause of the childrens sudden death, theyre trying to find a more affordable and accessible treatment.

"This is sort of phase 2 in this study, said Tester, who also authored the JAMA article.

To do that, the researchers turned to another novel approach: They engineered beating heart cells from blood samples donated by two people living with the condition.

He points to a cluster of heart cells undulating rhythmically under a microscope.

"These cells have the same exact genetic background that our patient does, he said. Here we can understand, at least from this patient's perspective what is the cell doing?"

Beating heart cells from blood samples donated by two people living with a condition that has caused the sudden death of Amish children.

Evan Frost | MPR News

In the coming months, Tester and his staff will perform a battery of tests on these cells, looking for clues that point them toward a better treatment.

But in the meantime, Mayo and Nemours continue to collaborate to understand just how common the condition is and how widespread. Their network has also extended to Iowa, where a genetic counselor is working with nearby Amish communities.

To ease that process, Mayo has made the test free for Amish families who may be affected.

Fitzgerald, the genetic counselor, is hopeful additional screening in Delaware and in other Amish communities will reveal more information about the condition.

And while she may not be able to offer her families a perfect solution today, at least they're starting to get some answers.

We don't want to give false hope, but I think it is important to tell families how far we come, she said. We tell people Hold on, stay tuned.

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Alteration in Expression of miR-32 and FBXW7 Tumor Suppressor in Plasm | CMAR – Dove Medical Press

Posted: February 19, 2020 at 12:45 am

Sanaz Mansouri,1,* Behzad Khansarinejad,2,* Ghasem Mosayebi,2 Aziz Eghbali,3 Mahdieh Mondanizadeh1,4

1Department of Biotechnology and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran; 2Department of Microbiology and Immunology, Arak University of Medical Sciences, Arak, Iran; 3Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran; 4Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

*These authors contributed equally to this work

Correspondence: Mahdieh MondanizadehDepartment of Biotechnology and Molecular Medicine, Arak University of Medical Sciences, Arak, IranTel/Fax +98-8634173526Email m_mondanizadeh@yahoo.com

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and malignant neoplasm that arises from the hematopoietic T-cell precursors. Inactivation of FBXW7 gene is frequently observed in T-cell acute lymphoblastic leukemia, suggesting a significant tumor-suppressive role for FBXW7 in the pathobiology of this leukemia. Considering the role of microRNAs in cell proliferation and regulation of apoptosis, the aim of this study was to identify novel oncogenic microRNAs that suppress FBXW7 in patients with T-ALL.Patients and Methods: The expression levels of two bioinformatically predicted microRNAs miR-32 and miR-107 were compared in patients with T-ALL and a control group. A total of 80 plasma samples were subjected to RNA extraction, and the microRNA expression profiles were assessed by the RT-qPCR. The expression level of miR-103 was used as the endogenous reference for normalization of quantitative data.Results: The plasma levels of miR-32 and miR-107 in patients with T-ALL were significantly higher (5.65, P< 0.001) and lower (0.432, P= 0.002), respectively. On the other hand, the expression levels of FBXW7 gene were significantly downregulated by 76.9 fold in T-ALL patients (P< 0.001). The results of the ROC curve analysis indicated that overexpression of miR-32 might be used to distinguish T-ALL patients with reasonable sensitivity and specificity.Conclusion: miR-32 is considered as a novel oncomir that targets FBXW7 and might have a role in the etiology or progression of T-ALL. Furthermore, miR-32 can potentially serve as a non-invasive biomarker for detection of T-ALL.

Keywords: biomarker, FBXW7, T-ALL, microRNA

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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The global cell expansion market is projected to reach US$ 42,837.11 Mn in 2027 from US$ 11,929.43 Mn in 2018 – GlobeNewswire

Posted: February 19, 2020 at 12:45 am

New York, Feb. 17, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Cell Expansion Market to 2027 - Global Analysis and Forecasts By Product ; Cell Type ; Application ; End User, and Geography" - https://www.reportlinker.com/p05862085/?utm_source=GNW

Cancer is one of the major cause of human death worldwide.In recent years, the cases of cancer have been increasing tremendously and the trend is anticipated to remain the same in the upcoming years.

According to the World Health Organization in 2018, approximately 9.6 million deaths across the globe were due to cancer. Furthermore, the National Cancer Institute predicted that in 2018, approximately 1,735,350 new cancer cases would be diagnosed in the US.

Changes in lifestyle have resulted in more exposure to oncogenic factors.Cancer can be cured if diagnosed and treated at an initial stage.

Cancer sequencing using next-generation sequencing (NGS) methods provides more information. Additionally, cell expansion related procedures also aids in research, diagnostics and treatment of cancer.Furthermore, Asia Pacific region is also facing the problem of the growing prevalence of cancer.The top 15 countries with Cancer prevalence are Japan, Taiwan, Singapore, South Korea, Malaysia, Thailand, China, Philippines, Sri Lanka, Vietnam, Indonesia, Mongolia, India, Laos, and Cambodia.

According to the National Institute of Cancer Prevention and Research (NICPR), in 2018, in India, total deaths due to cancer were 784,821.

The global Cell Expansion market is segmented by product, cell type, application, end user.Based on product, the cell expansion market is segmented into consumables and instruments.

In 2018, the consumables accounted for the largest market share in the global cell expansion market by product.These consumables are essential components of any laboratory experiment hence they are expected to witness significant growth during the forecast period.

Based on cell type, the cell expansion market has been segmented into human cell and animal cell.Furthermore based on application the cell expansion market has been segmented into Regenerative Medicine And Stem Cell Research, Cancer And Cell-Based Research and Other Applications.

Based in end user market is segmented into Biopharmaceutical And Biotechnology Companies, Research Institutes, cell banks and others.

Some of the essential primary and secondary sources included in the report are the National Institute of Cancer Prevention and Research (NICPR), Association for Management Education and Development, Center for Cancer Research, International Society for Stem Cell Research (ISSCR), American Association of Blood Banks (AABB), National Institute of Cancer Prevention and Research and others.Read the full report: https://www.reportlinker.com/p05862085/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The global cell expansion market is projected to reach US$ 42,837.11 Mn in 2027 from US$ 11,929.43 Mn in 2018 - GlobeNewswire

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Map of breast cancer reveals how mutations shape the tumour landscape – Pharmafield

Posted: February 19, 2020 at 12:45 am

Scientists have created a detailed map of breast cancer ever achieved, revealing how genetic changes shape the physical tumour landscape, according to research funded by Cancer Research UK and published in Nature Cancer.

An international team of scientists, brought together by an ambitious 20m Grand Challenge award from Cancer Research UK, has developed intricate maps of breast tumour samples, with a resolution smaller than a single cell.

These maps show how the complex cancer landscape made up of cancer cells, immune cells and connective tissue varies between and within tumours, depending on their genetic makeup.

This technique could one day provide doctors with an unparalleled wealth of information about each patients tumour upon diagnosis, allowing them to match each patient with the best course of treatment for them.

In the future, it could also be used to analyse tumours during treatment, allowing doctors to see in unprecedented detail how tumours are responding to drugs or radiotherapy. They could then modify treatments accordingly, to give each patient the best chance of beating the disease.

Dr Raza Ali, Lead Author of the study and Junior Group Leader at the Cancer Research UK Cambridge Institute, said: At the moment, doctors only look for a few key markers to understand what type of breast cancer someone has. But as we enter an era of personalised medicine, the more information we have about a patients tumour, the more targeted and effective we can make their treatment.

The researchers studied 483 different tumour samples, collected as part of the Cancer Research UK funded METABRIC study, a project that has already revolutionised our understanding of the disease by revealing that there are at least 11 different subtypes of breast cancer.

The team looked within the samples for the presence of 37 key proteins, indicative of the characteristics and behaviour of cancer cells. Using a technique called imaging mass cytometry, they produced detailed images, which revealed precisely how each of the 37 proteins were distributed across the tumour.

The researchers then combined this information with vast amounts of genetic data from each patients sample to further enhance the image resolution. This is the first time imaging mass cytometry has been paired with genomic data.

These tumour blueprints expose the distribution of different types of cells, their individual characteristics and the interactions between them.

By matching these pictures of tumours to clinical information from each patient, the team also found that the technique could be used to predict how someones cancer might progress and respond to different treatments.

Professor Carlos Caldas, Co-Author of the study from the Cancer Research UK Cambridge Institute, said: Weve shown that the effects of mutations in cancer are far more wide-ranging than first thought.

They affect how cancer cells interact with their neighbours and other types of cell, influencing the entire structure of the tumour.

The research was funded by Cancer Research UKs Grand Challenge initiative. By providing international, multidisciplinary teams with 20m grants, this initiative aims to solve the biggest challenges in cancer.

Dr David Scott, Director of Grand Challenge at Cancer Research UK said: This team is making incredible advances, helping us to peer into a future when breast cancer treatments are truly personalised.

Theres still a long way to go before this technology reaches patients, but with further research and clinical trials, we hope to unlock its powerful potential.

The researchers where based at the Cancer Research UK Cambridge Institute, University of Cambridge, the University of Zrich, Switzerland and the British Columbia Cancer Research Centre, Canada.

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