#Graphics in reverse Most recent advances in artificial intelligence such as mobile apps that convert speech to text are the result of machine learning, in
#New Way to Fight Cancer Targeted cancer therapies work by blocking a single oncogenic pathway to halt tumor growth.
But because cancerous tumors have the unique ability to activate alternative pathways, they are often able to evade these therapies and regrow.
Moreover, tumors contain a small portion of cancer stem cells that are believed to be responsible for tumor initiation, metastasis and drug resistance.
Thus, eradicating cancer stem cells may be critical for achieving long-lasting remission, but there are no drugs available that specifically attack cancer stem cells.
A Surprising Discovery Now a research team led by investigators at Harvard Medical school and the Cancer Center at Beth Israel Deaconess Medical center
has identified an inhibitor of the Pin1 enzyme that can address both these challenges in acute promyelocytic leukemia (APL) and triple-negative breast cancer.
Their surprising discovery demonstrates that the Vitamin a derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy,
can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme.
Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancerarticularly cancers that are aggressive
or drug resistant. in1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease,
explained co-senior author Kun Ping Lu, HMS professor of medicine and director of translational therapeutics in the Cancer Research Institute at Beth Israel Deaconess. in1 is a common key regulator in many types of cancer
and as a result can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells.
Lu also co-discovered the enzyme in 1996. A Different Approach Until now, agents that inhibit Pin1 have been developed mainly through rational drug design.
Although these inhibitors have proven active against Pin1 in the test tube when they are tested in vitro in a cell model
or in vivo in a living animal they are unable to efficiently enter cells to successfully inhibit Pin1 function.
In this new work, co-senior author Xiao Zhen Zhou, HMS assistant professor of medicine and an investigator in the Division of Translational Therapeutics at Beth Israel Deaconess, decided to take a different
approach to identify Pin1 inhibitors: She developed a mechanism-based high-throughput screen to identify compounds that were targeting active Pin1. e had identified previously Pin1 substrate-mimicking peptide inhibitors,
explained Zhou. e therefore used these as a probe in a competition binding assay and screened approximately 8,
in order to bind Pin1. hile it has been shown previously that ATRA ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL,
when two tumor suppressors fuse together to become an oncogene, added co-author Pier Paolo Pandolfi, the HMS George C. Reisman Professor of Medicine and director of the Cancer Genetics Program at Beth Israel Deaconess,
whose own pioneering work revealed the molecular underpinnings of APL and led to its cure. hese new findings demonstrate that by inhibiting Pin1,
you can degrade this fusion oncogene, thereby stopping cancer stem cells from replicating. This is a critically important discovery that will impact the treatment of other forms of cancer
since Pin1 inhibition is also affecting other key oncogenes. To that end, the authors also tested ATRA in triple-negative breast cancer, one of the most aggressive types of breast cancer.
They discovered that ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer growth in human cells and in animal models by simultaneously turning off many oncogenes and turning on many tumor suppressors.
Aiming at ream Targets These new results, say the authors, provide a rationale for developing longer half-life ATRA
or more potent and specific Pin1-targeted ATRA variants for cancer treatment. he current ATRA drug has a very short half life of only 45 minutes in humans,
and offers a promising new approach for targeting a Pin1-dependent common oncogenic mechanism in numerous cancer-driving pathways in cancer
and cancer stem cells. This is especially critical for treating aggressive or drug-resistant cancers. a
#Computer-Designed Rocker Protein Worlds First To Biomimic Ion Transport For the first time, scientists recreated the biological function of substrate transportation across the cell membranes by computationally designing a transporter protein.
such as targeting medicines more specifically into cancer cells and driving charge separation potentially for harvesting energy for batteries.
said Jean Chin of the National institutes of health National Institute of General Medical sciences, which funded the work through grants to several of the paper co-authors. he highly collaborative team used its deep knowledge of the structures,
and medicine. e envision that this protein can create an electrochemical gradient using things like ph,
According to the American Heart Association, African americans are at a higher risk than whites to die of heart disease.
Research over the last decade has demonstrated that discrimination against African americans may be a direct cause of many of these health problems
as well as information about stress and perceived discrimination through interviews. Goosby found a strong correlation between perceived discrimination and levels of C reactive-protein protein,
and blood pressure. didn expect that discrimination would have such a strong relationship with these particular markers of cardiovascular disease risk in kids this young,
#New transitional stem cells discovered Preeclampsia is a disease that affects 5 to 8 percent of pregnancies in America.
Complications from this disease can lead to emergency cesarean sections early in pregnancies to save the lives of the infants and mothers.
Scientists believe preeclampsia is caused by a number of factors, including shallow placentas that are associated insufficiently with maternal blood vessels.
Now, researchers from the University of Missouri, in an effort to grow placenta cells to better study the causes of preeclampsia,
and his colleagues, says these new stem cells can help advance research on preeclampsia and a number of other areas of the human reproductive process. hese new cells,
what causes diseases like preeclampsia and other prenatal problems. Embryonic stem cells are pluripotent, meaning they can develop into a number of different types of cells such as muscle cells, bone cells, skin cells, etc.
Says Study Angiogenesis inhibitors widely used class of cancer drugs designed to shrink tumors by preventing them from forming new blood vesselsften work in the short term,
and prevent cancer relapse. Working with laboratory models of pancreatic and breast cancer, the scientists found that myeloid cells,
and are part of the body first-line of defensehe so-called nnateimmune systemt first work in concert with the therapy
2015 online issue of Cell Reports, the researchers, under the direction of senior investigator Gabriele Bergers, Phd, UCSF professor of neurological surgery,
and first author Lee B. Rivera, Phd, a UCSF postdoctoral scholar in the Bergers laboratory, also identified a potential way to stop myeloid cells from sabotaging the therapy
they prevent the formation of new blood vessels. his is important in the early stages of wound healing,
During anti-angiogenic therapy, said Bergers, the Neill H. and Linda S. Brownstein Endowed Chair in Brain tumor Research and a member of the UCSF Helen Diller Family Comprehensive Cancer Center,
he tumor hijacks the second stage of the natural process we see in wound healing for its own advantage.
But we have learned that we can also manipulate this process to make therapy more effective.
which prevents the tumor from forming new blood vessels, thereby shrinking it. The researchers found that during the initial phase of therapy,
VEGF inhibition stimulates myeloid cells within the tumor to release the signaling protein CXCL14, which is angiostatic
and stimulates immunity. During this phase, myeloid cells complement the therapy to prevent the creation of new blood vessels,
and the tumor shrinks. But thenrobably in response to reduced oxygen flow within the tumoryeloid cells switch to their opposite state nd become real bad guys
said Bergers. At this stage the cells activate the PI3-kinase (PI3K) signaling pathway, which neutralizes CXCL14
and tumor growth. nce the PI3K pathway is activated, therapy becomes ineffective, and you have said relapse,
she. In breast cancer, Bergers noted, anti-VEGF therapy is not very effective to begin with. his tells us why,
she said. n a laboratory model of breast cancer, about 45 percent of myeloid cells are activated already,
so the cancer just ignores the therapy. The researchers found that targeting specific innate immune cells within the tumor did not reverse the negative effects of PI3K activation.
Eliminating macrophages one type of white blood cell resulted in an increase in neutrophils another type of white blood cell.
This so-called myeloid-cell oscillation maintained the tumor resistance to the therapy. Instead, said Bergers,
Ultimately, the researchers demonstrated that combining a PI3K inhibitor with anti-VEGF therapy prevented relapse
and significantly increased survival in a mouse model of pancreatic neuroendocrine tumor. Bergers noted that the discovery potentially gives physicians a way to determine how effective anti-VEGF therapy might be in individual patients
as well as to monitor the course of therapy. n some new patients, we could test to determine how many myeloid cells in the tumor were activated already,
which could tell us to what extent the tumor would still be responsive to anti-VEGF therapy,
she said. In patients undergoing therapy, e could take advantage of the fact that myeloid cells occur not only in the tumor,
but also in the blood, said Bergers. simple blood test would give us a noninvasive biomarker to check on the state of myeloid activation.
Right now, one of the major issues in anti-VEGF therapy is that there are no biomarkers for response and relapse. t
#Protein finding can pave the way for improved treatment of malignant melanoma Researchers from Aarhus University have linked for the first time a new protein with malignant melanomas.
The protein is detected in aggressive malignant melanoma cells and might be used to predict whether and how the cancer will spread.
At the same time, the discovery also opens new doors for future improved treatment of patients with melanomas.
Today it is not possible to predict spreading from malignant melanomas. Melanoma metastases are furthermore extremely difficult to eliminate as traditional treatment such as chemotherapy
and radiotherapy is mostly ineffective. Only ten per cent of the patients survive once they reach an advanced stage with distant metastases.
The discovery point towards the possibility of identifying aggressive melanomas at an earlier stage than is currently possible,
Pigment Cell & Melanoma Research. May be Possible to Predict Disease Progression It is the first time that the protein megalin,
which is known otherwise primarily for its function in the kidneys, has been connected with malignant melanomas. The novel knowledge is the result of longstanding research in the field of cell surface receptor proteins at the Department of Biomedicine at Aarhus University. ur studies have shown that the protein megalin is almost always detectable in malignant melanomas,
while it is rarely found in the benign counterparts. We see a clear trend that the more megalin is present
says Associate professor Mette Madsen from the Department of Biomedicine at Aarhus University. With the new knowledge, the hope is that pathologists
and oncologists at an early stage will be able unlike today to predict whether a patient should expect spreading
Even though we currently see considerable progress and success from novel treatment strategies for patients with metastatic melanoma,
it remains a very serious illness when it reaches later stages with spreading. In a best case scenario, this discovery can pinpoint those patients who will experience a relapse,
which patients the most, says Henrik Schmidt, consultant at the Department of Oncology at Aarhus University Hospital,
either medicine affecting the protein and its function thereby inhibiting the proliferation of the cancer cells and their survival,
and could easily be introduced at the hospitals
#Major Advance in Artificial Photosynthesis Poses Win/Win for the Environment A potentially game-changing breakthrough in artificial photosynthesis has been achieved with the development of a system that can capture carbon dioxide emissions before they are vented into the atmosphere
#Fruit fly studies shed light on adaptability of nerve cells An international team of researchers at German Center for Neurodegenerative Diseases (DZNE)
little was known about the signalling underlying such ynaptic plasticity Now, investigations of fruit flies by researchers at the German Center for Neurodegenerative Diseases (DZNE), Tokyo Tech, the National Institute of Genetics in Japan,
Future work may investigate how modifying the Wnt signal can be used to manipulate synaptic plasticity, with possible therapeutic applications for neurodegenerative or mental diseases n
said senior investigator Shingo Kajimura, Phd, UCSF assistant professor of cell and tissue biology, School of dentistry, with a joint appointment in the UCSF Diabetes Center and the Eli and Edythe Broad Center
of Regeneration Medicine and Stem Cell Research at UCSF. The finding was published online on March 16
2015 in Nature Medicine. All mammals, including humans, have two types of fat with completely opposite functions:
white, which stores energy and is linked with diabetes and obesity, and brown, which produces heat by burning energy
Typically, for a condition such as epilepsy, it is essential to act at exactly the right time and place in the brain.
enables localised inhibition of epileptic seizure in brain tissue in vitro. This research is published in the journal Advanced Materials.
Drugs constitute the most widely used approach for treating brain disorders. However, many promising drugs failed during clinical testing for several reasons:
Epilepsy is a typical example of a condition for which many drugs could not be commercialised because of their harmful effects,
when they might have been effective for treating patients resistant to conventional treatments 1. During an epileptic seizure,
have developed a biocompatible micropump that makes it possible to deliver therapeutic substances directly to the relevant areas of the brain.
the researchers reproduced the hyperexcitability of epileptic neurons in mouse brains in vitro. They then injected GABA,
In addition to epilepsy this state-of-the-art technology, combined with existing drugs, offers new opportunities for many brain diseases that remain difficult to treat at this time a
#Yale scientists apply new tool to explore mysteries of the immune system Why do infected some individuals with the West nile virus develop life-threatening infections
while others never know they had more than a mosquito bite? That medical mystery is just one of the questions that Ruth Montgomery,
associate professor of medicine at Yale School of medicine, seeks to explore with the use of a transformational tool for translational research.
It called Cytof, which stands for cytometry by time-of-flight, and it gives researchers greater insight into the intricacies of immune cells than ever before.
researchers studying a range of conditions from West Nile to multiple sclerosis to diabetes to cancer can generate an unprecedented level of detailed data about cells from relatively small samples.
deepening their understanding of cell biology and human disease. SPADE analysis showing the multiple subsets of immune and nonimmune cells that Cytof technology can detect from a single sample.
It akin to the difference between looking at the stars with a standard telescope versus an observatory-quality refractor telescope, according to Yale chair of neurology, Dr. David Hafler, who worked with Montgomery to bring Cytof to Yale. t allows
Montgomery applies the technology to her study of how aging impacts the immune response to infections and autoimmune diseases.
The research may help explain differences in immune response to infection that could potentially benefit those most harmed by the illness, notes Montgomery.
Similarly, in his lab, Hafler applies Cytof to the study of cellular complexities at the root of diseases such as a multiple sclerosis and cancer.
In one current project, his team is investigating specific types of immune cells extracted from brain tumors. ee isolating T cells from brain tumors,
Understanding how multiple molecules function at the same time in a single cell may reveal clues about how brain tumors manage to survive
he said. he more we can define how the tumor is evading the immune system, the more specific we can make the treatment.
we can be more precise in defining the therapy moving forward. Eye on immune therapies and prevention In his lab, professor of immunology Dr. Kevan Herold has used the technology to explore key questions about type 1 diabetes, an autoimmune condition.
Cytof is helping his team get more data about a limited repertoire of cells specific to type 1 diabetes
which typically appears during childhood. e want to understand the targets of the cells that cause diabetes,
he said. hat turns them on? What turns them off? are involved there pathways that we can target for therapies?
Those are the types of questions wee interested in. The goal is not only to develop immune therapy to treat type 1 diabetes
but potentially to use the data for prevention. here are antigen-reactive T cells that are found in individuals at risk for type 1 diabetes,
said Herold. ome of those individuals go on to develop diabetes; others don. What we want to do is figure out who is going to go on to develop diabetes
in order to prevent it. If he identifies a marker that differentiates between patient types, for example, that finding could point to a target for preventive strategies, notes Herold.
The work of Montgomery, Hafler, and Herold may be just the tip of the iceberg. With this more powerful tool for analyzing cells,
and profile whole populations of immune cells for the study of cancer and other complex diseases.
and the immune therapies that emerge. e tend to think of our analyses of cells as unidimensional or bi-dimensional.
diseases and higher temperatures and droughts expected to accompany climate change. Cotton growers have experienced a plateau in yields since the early 1990s
and breeders in the years ahead develop cotton varieties with improved fiber qualities, higher yields and more tolerance to heat, drought and diseases anticipated due to climate change.
with applications for everything from fuel cells to biological implants. t a huge step for nanofabrication, said Jan Schroers, professor of mechanical engineering and materials science at Yale,
#An end to cancer pain? U of T researcher finds the ain trigger A new study led by University of Toronto researcher Dr. David Lam has discovered the trigger behind the most severe forms of cancer pain.
Released in top journal Pain this month, the study points to TMPRSS2 as the culprit:
a gene that is also responsible for some of the most aggressive forms of androgen-fuelled cancers.
Head of Oral and Maxillofacial Surgery at the Faculty of dentistry, Lam research initially focused on cancers of the head and neck,
Studies have shown that these types of cancers are the most painful, with sufferers experiencing pain that is immediate and localized,
and neck cancer patients are men leading him to investigate a genetic marker with a known correlation to prostate cancer,
TMPRSS2. rostate cancer research already knows that if you have the TMPRSS2 gene marker, the prostate cancer is much more aggressive.
Theye also shown that this is androgen (male hormone) sensitive. In his study, Lam, who is appointed jointly as a Consultant Surgeon at the Princess Margaret Cancer Centre
and a Clinician at the Mount sinai Wasser Pain Management Centre, ascertained that TMPRSS2 was not only present in patients suffering from head
and neck cancers it was also prevalent in much greater quantities than in prostate cancer.
Lam and his fellow researchers followed up this observation by looking at different types of cancers with known pain associations for instance, certain breast and melanoma cell lines.
and neck cancer is the most painful form of cancer, followed by prostate cancer, while melanoma,
or skin cancer, sits at the bottom of the pain scale. But what surprised the researchers was that the presence
and amount of TMPRSS2 in these cancer cell cultures stood in exact correlation with the known level of pain each cancer causes. t was exactly
what we know clinically about pain association, adds Lam. A New Direction for Drug Research The startling discovery of TMPRSS2 role in triggering cancer pain may lead to the creation of targeted cancer pain therapies that effectively shut down the expression of this gene
or its ability to infiltrate pain receptors in the body. Dr. Brian Schmidt, Professor at New york University college of Dentistry, Director of the Bluestone Center for Clinical Research and a co-author of the study states,
he discovery that TMPRSS2 drives cancer pain demonstrates another way that cancers lead to suffering.
Inhibition of its activity in patients might provide a new form of treatment for cancer pain. ny cancer that is painful before initiating drug treatment we can label the cancer cells for TMPRSS2
what role the increased expression of TMPRSS2 plays in the aggressiveness and morbidity rates associated with certain aggressive cancers
#Researchers get under the skin to develop new transplant technique James Shapiro, one of the world leading experts in emerging treatments of diabetes, can help
but be excited about his latest research. The results, he says, could soon mark a new standard for treatmentot only for diabetes,
but for several other diseases as well. Shapiro, Canada Research Chair in Transplantation Surgery and Regenerative medicine in the University of Alberta Faculty of medicine & Dentistry,
and Andrew Pepper, a postdoctoral fellow working in his lab, are the lead authors in a study published in the April 20 edition of the journal Nature Biotechnology.
In the study the authors describe developing a new site for islet transplantation under the skin,
Islet transplantation is a procedure that temporarily allows people with severe diabetes to stop taking insulin. ntil now it has been nearly impossible for transplanted cells to function reliably
we have successfully and reliably reversed diabetes in our preclinical models. This approach is new
not only in diabetes, but also across the board in regenerative medicine. Evolving the Edmonton Protocol The new technique, tested in preclinical models,
is an evolution of the Edmonton Protocol, which Shapiro developed in the late 1990s to treat Type 1 diabetes.
In the Edmonton Protocol, islet cells are transplanted into the liver, granting patients insulin independence for a varying amount of time.
we need a better, safer site to implant experimental cells. The skin offers a remarkable opportunity,
While the new transplant approach offers several benefits to diabetes patients, the researchers are excited equally by how it may be applied to other illnesses.
his exciting new approach doesn have to be limited to diabetes. For any area of regenerative medicine that requires replacing old cells with newnd there lots of different disease states where there just one gene defect that could be corrected by a cell transplanthis opens up an incredible future possibility for successful engraftment beneath the skin.
Shapiro has filed a patent for the new transplant technique and hopes to begin human trials in the very near future t
#Engineering the Smallest Crack in the World A new procedure will enable researchers to fabricate smaller, faster,
Structures with these well-defined, atomic-sized gaps could be used to detect single molecules associated with certain diseases
particularly those that are characteristic of certain diseases. When light is shined upon structures with extremely small gaps,
This enhanced electromagnetic field, in turn, increases the signal produced by any molecule within the gap. f some disease marker comes in and bridges the gap between the nanostructures
whether the disease was present or not, said Lipomi. While the technique reported in this study can produce nanostructures suitable for optical applications,
#Researchers'"hugely exciting"asthma discovery Cardiff scientists have identified for the first time the potential root cause of asthma and an existing drug that offers a new treatment.
Published today in Science Translational Medicine journal, University researchers, working in collaboration with scientists at King College London
and the Mayo Clinic (USA), describe the previously unproven role of the calcium sensing receptor (Casr) in causing asthma,
a disease which affects 300 million people worldwide. The team used mouse models of asthma and human airway tissue from asthmatic and non-asthmatic people to reach their findings.
Crucially, the paper highlights the effectiveness of a class of drugs known as calcilytics in manipulating Casr to reverse all symptoms associated with the condition.
cigarette smoke and car fumes and airways twitchiness in allergic asthma. ur paper shows how these triggers release chemicals that activate Casr in airway tissue
and drive asthma symptoms like airway twitchiness, inflammation, and narrowing. Using calcilytics, nebulized directly into the lungs,
Director of research and Policy at Asthma UK, who helped fund the research, said: his hugely exciting discovery enables us, for the first time,
to tackle the underlying causes of asthma symptoms. Five per cent of people with asthma don respond to current treatments so research breakthroughs could be life changing for hundreds of thousands of people. f this research proves successful we may be just a few years away from a new treatment for asthma,
and we urgently need further investment to take it further through clinical trials. Asthma research is chronically underfunded;
there have only been a handful of new treatments developed in the last 50 years so the importance of investment in research like this is absolutely essential.
While asthma is controlled well in some people, around one-in-twelve patients respond poorly to current treatments.
the identification of Casr in airway tissue means that the potential for treatment of other inflammatory lung diseases beyond asthma is immense.
for which currently there exists no cure. It is predicted that by 2020 these diseases will be the third biggest killers worldwide.
Professor Riccardi and her collaborators are now seeking funding to determine the efficacy of calcilytic drugs in treating asthmas that are especially difficult to treat,
particularly steroid-resistant and influenza-exacerbated asthma, and to test these drugs in patients with asthma.
Calcilytics were developed first for the treatment of osteoporosis around 15 years ago with the aim of strengthening deteriorating bone by targeting Casr to induce the release of an anabolic hormone.
Although clinically safe and well tolerated in people calcilytics proved unsuccessful in treating osteoporosis . But this latest breakthrough has provided researchers with the unique opportunity to re-purpose these drugs,
potentially accelerating the time it takes for them to be approved for use asthma patients. Once funding has been secured,
the group aim to be trialling the drugs on humans within two years. f we can prove that calcilytics are administered safe
when directly to the lung in people, then in five years we could be in a position to treat patients
and potentially stop asthma from happening in the first place, added Professor Riccardi. The study was part-funded by Asthma UK
the Cardiff Partnership Fund and a BBSRC parking Impactaward d
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