#Scientists dramatically improve method for finding common genetic alterations in tumors St jude Children's Research Hospital scientists have developed a significantly better computer tool for finding genetic alterations that play an important role in many cancers
The comparison involved the normal and tumor genomes from 43 children and adults with brain tumors, leukemia, melanoma and the pediatric eye tumor retinoblastoma."
whole-genome sequencing to better understand the genetic landscape of cancer genomes and lay the foundation for the next era of cancer therapy,
"said corresponding author Jinghui Zhang, Ph d.,a member of the St jude Department of Computational biology.""In this study of the tumor and normal genomes of 43 patients, CONSERTING identified copy number alterations in children with 100 times greater precision and 10 times greater precision in adults."
"First author Xiang Chen, Ph d.,a St jude senior research scientist, added:""CONSERTING helped us identify alterations that other algorithms missed,
and copy number alterations present in a small percentage of tumor cells.""Using CONSERTING, researchers discovered genetic alterations driving pediatric leukemia, the pediatric brain tumor low-grade glioma, the adult brain tumor glioblastoma and retinoblastoma.
The algorithm also helped identify genetic changes that are present in a small percentage of a tumor's cells.
The alterations may be the key to understanding why tumors sometimes return after treatment. In addition, Zhang said CONSERTING should make it easier to track the evolution of tumors with complex genetic rearrangements,
sometimes involving multiple chromosomes that swap pieces when they break and reassemble. St jude has made CONSERTING available for free to researchers worldwide.
The software user manual and related data can be downloaded from http://www. stjuderesearch. org/site/lab/zhang.
scientists can upload data for analysis. Work on CONSERTING began in 2010 shortly after the St jude Children's Research Hospital--Washington University Pediatric Cancer Genome Project was launched.
The Pediatric Cancer Genome Project used next-generation, whole-genome sequencing to study some of the most aggressive and least understood childhood cancers.
and provide insight into the origins of a patient's cancer. CONSERTING has now been used to analyze next-generation,
whole-genome sequencing data for the Pediatric Cancer Genome Project. The project includes the normal and cancer genomes of 700 pediatric cancer patients with 21 different cancer subtypes.
CONSERTING combines a method of data analysis called regression tree, which is a machine learning algorithm, with next-generation,
even those present in relatively few cells or in tumor samples that include normal cells along with tumor cells,
This is the first time a large therapeutic protein like catalase has been delivered to the brain using exosomes. Getting drugs into the brain is extremely difficult in general
Diseases like cancer and AIDS propagate throughout the body by hijacking exosomes.""Exosomes are engineered by nature to be the perfect delivery vehicles for proteins and genetic material,
"Traditional drugs--from cold medicine to chemotherapy--are composed of small molecules of a few dozen atoms, typically.
These packages of medicine will be ignored by the patient's immune system, which works against unknown proteins as well as many synthetic delivery vehicles s
As the spool pulls, the CNT ribbon is dragged between two surgical blades. While the blades appear straight to the naked eye,
#Breast cancer vaccines may work better with silicon microparticles Model studies showed that microparticles loaded with an antigen, HER2,
not only protected the antigen from premature destruction, but also stimulated the immune system to recognize and relentlessly attack cancer cells overexpressing the HER2 antigen."
"We could completely inhibit tumor growth after just one dose of the cancer vaccine in the animal model,
"said principal investigator Haifa Shen, M d, . Ph d."This is the most amazing result we have seen ever in a tumor treatment study."
"The success of the treatment, Shen and his team learned, appears to be the porous silicon microparticles (PSMS) themselves.
In vivo and in vitro studies confirmed the microparticles stimulated a strong, sustained innate immune response at local sites of tumor activity and growth--with or without any antigen loaded."
"We have shown for the first time that a microparticle can serve as a carrier for sustained release and processing of tumor antigens,
and were transferred even from one antigen-presenting cell to another to maintain a long-lasting antigen-releasing effect."
"Cancer vaccines are designed to turn a patient's own immune system more strongly against cancer cells, and have been an area of recent and intense interest among oncologists.
Since 2010, the FDA has approved vaccines and other immunotherapy drugs for melanoma, prostate cancer, and lung cancer.
There are currently dozens of active clinical trials evaluating vaccines for cancer therapy. Approximately 235,000 new diagnoses of breast cancer were made last year,
and over 40,000 patients died from the disease. As yet, there are no FDA-approved vaccines for breast cancer.
Such a vaccine might target HER2 a cell surface hormone receptor that is overexpressed in the tumor cells of 15 to 30 percent of breast cancer patients.
Such cells are called HER2+or HER2 positive. In this case, HER2 is both a naturally occurring hormone receptor and an antigen target for therapy.
A vaccine against HER2 would train the immune system's more destructive agents to recognize the cancer cells overproducing HER2
and destroy them, leaving healthy cells more or less alone. But so far, vaccines against HER2 have seen only moderate success."Vaccines targeting the HER2 oncoprotein have been tried,
"Shen said.""But these vaccines have mostly not been very potent because of inefficient vaccine delivery, a poor immune response at the site of the tumor,
and other factors. We have shown that the PSM-mediated vaccine is not only potent enough to trigger tumor cell killing,
but also modifies the tumor microenvironment in a way that favors tumor treatment.""An important aspect of PSM function is stimulating the body's own immune system to fight cancer,
Shen said.""PSMS persistently challenge the antigen-presenting cells to activate the T cells, "he said."
"And the PSMS modify the tumor microenvironment so that the cytotoxic T cells maintain their activity.""Shen said the use of PSMS could work for any variety of cancer antigens and cancers,
and that the PSMS could be loaded with multiple antigens for a single vaccine target, or multiple antigens for several targets, possibly enhancing the approach's effectiveness further."
"Besides developing a highly potent breast cancer vaccine, we have demonstrated also that PSMS are said versatile, "Shen."
"This is a technology platform that can be applied by other scientists to develop vaccines for other types of cancers, ultimately helping,
we hope, more types of cancer patients.""Before human clinical trials can begin, Shen said the researchers must evaluate the toxicity of antigen-loaded PSMS s
#Enzyme responsible for obesity-related high blood pressure identified"Hypertension is a condition in which arterial blood vessels are exposed to persistently elevated blood pressure,
making the heart work harder to pump blood to the body, "said William Durante, a professor of medical pharmacology and physiology at the MU School of medicine and lead author of the study."
"Hypertension can lead to severe health issues such as heart attacks, kidney failure, organ damage, and weakened or ruptured blood vessels.
By comparing genetically obese rats to lean rats, we discovered that obese animals were deficient in the amino acid arginine due to elevated activity of the enzyme arginase,
which breaks down this molecule.""Although arginase is present throughout the body, it is primarily found in the liver.
Its role is to assist in the breakdown of ammonia, which is flushed eventually out during urination.
However, Durante's team found significantly increased arginase activity within blood vessels and in the blood of obese rats compared to lean animals."
"The problem with this development is that arginase depletes arteries and blood of arginine, which is needed to generate nitric oxide,
"Durante said.""Nitric oxide is formed a gas from arginine that relaxes blood vessels and lowers arterial blood pressure.
The destruction of arginine by arginase reduces nitric oxide levels, leading to the constriction of blood vessels and high blood pressure."
Although both approaches restored nitric oxide production and reversed hypertension in obese rats, the use of arginase-inhibiting drugs may be a better solution."
"Blocking arginase activity offers a more specific approach in treating hypertension, because you are directly targeting the underlying biochemical defect in obesity,
However, Durante feels that identifying the role of arginase in the development of obesity-related hypertension will ultimately benefit obese patients."
"The key to reversing the effects of obesity-related hypertension will be to effectively block arginase activity.
"This deeper understanding of decision-making will help researchers to fine-tune the control algorithms of neural prostheses to enable people with paralysis to drive a brain-controlled prosthetic arm or guide a neurally-activated cursor on a computer screen.
and Stephen I. Ryu, now a consulting professor of electrical engineering at Stanford and a neurosurgeon at the Palo alto Medical Foundation.
X-ray computer tomography (CT) has become an important diagnostic tool in medicine. Conventional CT SCANS are very detailed
"says Professor for Biomedical Physics Franz Pfeiffer of the Technical University of Munich in Germany, who led the new study published April 20 in the Proceedings of the National Academy of Sciences."
these methods require X-ray light with a well-defined wavelength aligned in a particular way--properties that conventional CT SCANNERS in hospitals do not deliver sufficiently.
--but these are large and expensive machines that cannot simply be implemented at every research institute and clinic.
Implications for Cancer, Materialsthe success of this research, which was done on a CLS prototype, has led to the commissioning of the first commercial device.
and dark-field CT in preclinical studies--an approach that could help visualize cancer.""We work closely together with two clinics to study tumors,
"Eggl says.""One of our plans is to image breast tissue samples and also entire breasts after mastectomy to better understand the clinical picture of breast cancer."
"Besides medical applications, multimodal tomography could also open up new possibilities in materials science, for instance, in studies of extremely durable and lightweight carbon fibers and other fibrous materials,
the results show that the pyrolysis of manure waste has other additional environmental benefits such as reduced soil nutrient leaching and less waste volume, removal of odor and pathogens of the original material.
#Bacteria research opens way for new antibiotics University of Adelaide researchers have discovered a target for the development of completely new antibiotics against disease-causing bacteria.
which act as weapons to cause disease, such as toxins or degrading enzymes). The building block, called the Passenger-associated Transport Repeat (PATR),
and Meningococcus as well as bacteria that cause infections in cystic fibrosis and burns patients. It has been found in many of the major so-called'Gram negative bacteria,
where they need to be to function as disease-causing agents.""Bacteria can only cause disease
when virulence factors are produced appropriately by the bacteria and transported (or secreted) onto the cell surface where they become harmful,
"Our results are very exciting#we are not just talking about one molecule in one particular pathogen but rather a building block
The latest findings follow more than a decade of work led by Associate professor Renato Morona looking at how bacteria cause disease.
what scale,"explains Sophia Zackrisson and Kristina Lång, radiologists at Skåne University Hospital in Malmö and researchers at Lund University.
meaning more healthy women with benign lesions were recalled for further testing. This is a drawback in screening,
as it can cause unnecessary psychological stress. The ongoing research will also look at costs. Breast tomosynthesis is a somewhat more expensive technique."
"The UC Berkeley engineers teamed up with Dr. Thomas Nutman from the National Institute of Allergy and Infectious diseases,
or parasitic worm, diseases onchocerciasis (river blindness) and lymphatic filariasis. The video Cellscope, which uses motion instead of molecular markers
May 6, in the journal Science Translational Medicine.""This research is addressing neglected tropical diseases, "said Fletcher."
"It demonstrates what technology can do to help fill a void for populations that are suffering from terrible, but treatable diseases."
"Battling parasitic wormsriver blindness is transmitted through the bite of blackflies and is the second leading cause of infectious blindness worldwide.
Lymphatic filariasis, spread by mosquitoes, leads to elephantiasis, a condition marked by painful, disfiguring swelling in parts of the body.
It is the second leading cause of disability worldwide and, like river blindness, is highly endemic in certain regions in Africa.
The antiparasitic drug ivermectin, or IVM, can be used to treat these diseases, but mass public health campaigns to administer the medication have been stalled because of potentially fatal side effects for patients co-infected with Loa loa,
which causes loiasis, or African eye worm. When there are high circulating levels of microscopic Loa loa worms in a patient,
treatment with IVM can lead to brain or other neurologic damage that can be severe or fatal.
The standard method of screening for levels of Loa loa involves trained technicians manually counting the worms in a blood smear using conventional laboratory microscopes,
making the process impractical for use in field settings and in mass campaigns to administer IVM.
representing a major setback in the efforts to eradicate river blindness and elephantiasis. Next generation Cellscope uses video, automationfor this latest generation of the mobile phone microscope, named Cellscope Loa, the researchers paired a smartphone with a 3d printed plastic base where the sample of blood
"The availability of a point-of-care test prior to drug treatment is a major advance in the control of these debilitating diseases,
#Photoactive dye could prevent infection during bone-repair surgery Despite extensive procedures to sterilize small and large bone fragments used in joint replacement or reconstructive surgeries,
the rate of infection remains around 5 percent and can reach 11 percent or even higher in bone repairs for gunshot wounds or reconstruction after tumor removal.
Infection after surgery is a serious complication that can require further surgery and can be life threatening.
A new study demonstrates for the first time that an antimicrobial dye activated by light avidly adheres to bone to prevent bacteria from growing on bone fragments used in reconstructive surgery
and remove any bacteria that has attached already, thereby sterilizing the bone for surgery. The study was published online April 17 ahead of print in the journal of Clinical Orthopaedics and Related Research."
"We used a class of chemicals called porphyrins that are tolerated very well by the body in the dark
and appear to have excellent antimicrobial properties in the presence of light, "says Noreen Hickok, Ph d.,Associate professor of Orthopedic Surgery at Thomas Jefferson University."
"These properties allow sterilization during surgical procedures, which occur in bright light.""Surgeons often use bone chips
or bone powder as a sort of putty during bone reconstruction to help areas of bone re-grow.
when a tumor or accident requires replacement of a large segment of bone. These bone materials can come either from the patient
the TAPP dye could be added to the currently used protocols for sterilizing the bone prior to use in surgery."
and the other would be the continuation of the activation in the bright lights of the surgical suite
so that the sterilizing effects of the ROS release could continue well into surgery and implantation,"says Dr. Hickok."
"We need to continue testing in conditions that more closely resemble the surgical suite, but we think that this method could offer a more effective method to help improve patient outcomes by reducing infection rates
#Smarter, cheaper technologies offer improved point-of-care medicine A team from Stanford university School of medicine (Bio-Acoustic MEMS in Medicine Labs) developed assays for the simple and rapid detection
of HIV-1, various bacteria, and CD4+T lymphocytes. The assays for pathogens and cells were used as proof of concept to demonstrate the utility of several new detection and sensing technologies.
Overall, the group has developed platforms and sensing devices that are easy to make, easy to use and can be disposed safely of after use--characteristics necessary for developing affordable tools with broad applications in both developed and developing countries.
"The group is simultaneously developing multiple novel methods that target important diseases in underserved communities,
inexpensive technologies that can be applied to a wide range of health care problems and settings.""Testing for HIV-1 in whole bloodcurrent tests for HIV infection detect antibodies to HIV in the individual's blood.
However, because it takes up to several months for those antibodies to form, these tests do not detect individuals in the earliest stage of infection
when they are most likely to pass on the disease. In order to detect HIV-1 in recently infected individuals the researchers developed an assay that can detect the presence of the virus in whole blood or plasma.
The platform is a disposable flexible polyester chip with implanted electrodes. HIV-1 antibodies are added to whole blood
or plasma where they bind to the virus creating aggregates of antibody and viral lysate.
When added to the flexible chip the aggregates change the electrical conductivity of the chip, which gives a simple electrical readout indicating that the sample contains HIV-1.
In addition to detecting early stage infection, the electrical readout is much simpler and less expensive than current assays.
The researchers estimate that the cost is about $2 per test and can be disposed safely of after use.
CD4+T lymphocyte capture and detectionaccurate CD4+T cell count is essential for HIV-1 diagnosis and treatment monitoring.
World health organization guidelines recommend antiretroviral therapy for individuals with a CD4+T cell count of less than 500 cells/ml.
The microfluidic channels were coated with an antibody that captures the CD4+T cells. A single drop of whole blood from a fingerprick was applied to the polyester film,
and S. aureus are the most common bacterial pathogens that cause food poisoning, skin infections and blood infections.
The group developed a sensitive biosensing platform that detects E coli by the aggregation of nanoparticles on cellulose Paper gold nanoparticles are covered with surface molecules that bind to E coli bacteria.
of the Demirici Bio-Acoustic-MEMS in Medicine Laboratory at Stanford School of medicine,"is to simplify the techniques that both capture the biotarget
These platform technologies can be applied potentially broadly to other diseases such detecting oncogenic viruses such as KSHV, HPV, HBV and HCV,
#3d'organoids'grown from patient tumors could personalize drug screening Three-dimensional cultures (or'organoids')derived from the tumors of cancer patients closely replicate key properties of the original tumors,
reveals a study. These'organoid'cultures are amenable to large-scale drug screens for the detection of genetic changes associated with drug sensitivity
and pave the way for personalized treatment approaches that could optimize clinical outcomes in cancer patients."
"This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumors,
"says senior study author Mathew Garnett, a geneticist at the Wellcome Trust Sanger Institute.""We believe that these organoids are an important new tool in the arsenal of cancer biologists
and may ultimately improve our ability to develop more effective cancer treatments.""To study the causes of cancer
and develop new cancer treatments, many laboratories use experimental model systems such as cells grown from patient tumors.
However, currently available cell lines have been derived under suboptimal conditions and therefore fail to reflect important features of tumor cells.
As a result, it has been challenging to predict the drug sensitivity of individual patients based on their unique spectrum of genetic mutations.
In recent years, scientists have developed organoid cell culture systems as an alternative approach to grow normal and diseased tissue in a dish.
In contrast to cell lines organoids display the hallmarks of the original tissue in terms of its 3d architecture,
whether these cultures could potentially bridge the gap between cancer genetics and patient outcomes. In the new study, the researchers grew 22 organoids derived from tumor tissue from 20 patients with colorectal cancer
and then sequenced genomic DNA isolated from these cultures. The genetic mutations in the organoid cultures closely matched those in the corresponding tumor biopsies and agreed well with previous large-scale analyses of colorectal cancer mutations.
These findings confirm that the cultures faithfully capture the genomic features of the tumors from
which they are derived as well as much of the genomic diversity associated with colorectal cancer. To link drug sensitivity to genetic changes,
the researchers next screened the responses of the organoids to 83 experimental and approved cancer drugs.
indicating that the subset of cancer patients with RNF43 mutations would strongly benefit from a drug that inhibits a protein called porcupine."
"At some point in the future, this approach may be suitable for modeling individual patient response to cancer therapies to inform clinical treatment,
Moving forward, the researchers plan to expand the panel of existing colon organoids as well as develop an organoid biobank for other tumor types."
"Cancer is a diverse and complex disease and having a large collection of organoids is necessary to encompass this diversity to enable scientists
By increasing the stiffness of erythrocytes infected by the causal agent of malaria, Viagra favors their elimination from the blood circulation
and Tropical Medicine, could lead to a treatment to reduce the spread of malaria within a population.
Their work is published in PLOS Pathogens on 7 may 2015. Plasmodium falciparum the parasite that causes malaria, has a complex developmental cycle that is partially completed in humans and partially in the anopheline mosquito.
Treatments for malaria target the asexual forms of this parasite that cause symptoms, but not the sexual forms transmitted from a human to a mosquito when it bites.
Eradication of this disease thus necessitates the development of new types of treatments against sexual forms of the parasite
in order to block transmission and thus prevent dissemination of the disease within the population. The sexual forms of the parasite develop in human erythrocytes sequestered in the bone marrow before they are released into the blood.
They are then accessible to mosquitoes which can ingest them when they bite (see the top of the image on page 2)
This discovery could help find new ways to stop the spread of malaria in a population.
#Urine test for early stage pancreatic cancer possible after biomarker discovery A team at Barts Cancer Institute, Queen Mary University of London, has shown that the three-protein'signature'can both identify the most common
--and distinguish between this cancer and the inflammatory condition chronic pancreatitis, which can be hard to tell apart.
while patients suffering from chronic pancreatitis had significantly lower levels than cancer patients. When combined, the three proteins formed a robust panel that can detect patients with stages I-II pancreatic cancer with over 90 per cent accuracy.
With few specific symptoms even at a later stage of the disease, more than 80 per cent of people with pancreatic cancer are diagnosed
when the cancer has already spread. This means they are not eligible for surgery to remove the tumour--currently the only potentially curative treatment.
The five-year survival rate for pancreatic cancer in the UK is the lowest of any common cancer, standing at 3 per cent.
This figure has improved barely in 40 years. There is no early diagnostic test available. Lead researcher, Dr Tatjana Crnogorac-Jurcevic, said:"
people at higher risk of developing the disease include those with a family history of pancreatic cancer, heavy smokers, the obese and people over 50 years with new-onset diabetes.
if the 3-biomarker signature is present during the latency period--the time between the genetic changes that will cause the cancer to develop and the clinical presentation."
"For a cancer with no early stage symptoms, it's a huge challenge to diagnose pancreatic cancer sooner,
"says co-author and Director of Barts Cancer Institute, Professor Nick Lemoine.""With pancreatic cancer, patients are diagnosed usually
when the cancer is already at a terminal stage, but if diagnosed at stage 2,
Early diagnosis is an important part of our overall efforts against this aggressive cancer, alongside developing new treatments to tackle the disease once diagnosis is made.
It underlines the importance of increased research efforts to help improve survival rates.""Many of the urine samples from healthy individuals tested by Tanja's team were donated from the charity's own supporter community,
3-D printed'tissue'to help combat disease A bench-top brain that accurately reflects actual brain tissue would be significant for researching not only the effect of drugs,
but brain disorders like schizophrenia, and degenerative brain disease. Researchers have completed now 3-D printing a six-layered structure similar to brain tissue, in
which cells are placed accurately and remain in their designated layer. Researchers at the ARC Centre of Excellence for Electromaterials Science (ACES) have taken a step closer to meeting this challenge,
Pharmaceutical companies spend millions of dollars testing therapeutic drugs on animals only to discover in human trials that the drug has an altogether different level of effectiveness.
but brain disorders like schizophrenia, and degenerative brain disease. ACES Director and research author Professor Gordon Wallace said that the breakthrough is significant progress in the quest to create a bench-top brain that will enable important insights into brain function,
in addition to providing an experimental test bed for new drugs and electroceuticals.""We are still a long way from printing a brain
Various sight recovery therapies are being developed by companies around the world, offering new hope for people who are blind.
what vision would be like after two different types of sight recovery therapies. Lead author Ione Fine,
if they undergo sight restoration surgery, an invasive and costly procedure.""This is a really difficult decision to make,
"These devices involve long surgeries, and they don't restore anything close to normal vision. The more information patients have, the better."
Loss of rods and cones is the primary cause of vision loss in diseases such as macular degeneration or retinitis pigmentosa.
But those diseases leave most remaining neurons within the retina relatively intact, and various technologies under development aim to restore vision by targeting the surviving cells.
Fine said better simulations can provide valuable information about how implants need to be improved to produce more natural vision."
we're just shooting in the dark in trying to improve these implants
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