The findings could have therapeutic implications specific to this rare form of the disease, say the authors.
Research from Rutgers Cancer Institute of New jersey shows genomic profiling identifies genomic mutations in a gene associated with a rare subset of breast cancer--mutations that cannot otherwise be identified with standard clinical analysis of cells and tissue.
being presented as part of a poster presentation at the Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia,
could have therapeutic implications specific to this rare form of the disease, say the authors.
Invasive lobular carcinoma is a cancer that starts in the lobules, an area of the breast where milk is produced.
Pleomorphic invasive lobular carcinoma is a unique subset of lobular breast cancer that has abnormally aggressive tumor cells and results in poorer outcomes than the classic lobular breast cancer.
which is tested routinely for using standard pathologic techniques. As part of the precision medicine initiative at the Cancer Institute of New jersey, investigators--which include colleagues from Rutgers Robert Wood Johnson Medical school and RUCDR Infinite Biologics, the world's largest university-based biorepository,
located within the Human genetics Institute of New jersey--wanted to define the relationship of ERBB2 alterations in the pleomorphic form of the disease."
"Figuring out specific differences that are not visible under the microscope allows us to intervene with more appropriate and potentially lifesaving therapy.
With genomic sequencing detecting ERBB2 alterations in this form of cancer, we have an opportunity to identify anticancer therapies that would specifically target that abnormality
and that would otherwise not be given to those patients who could benefit. These genomic abnormalities would be overlooked with current,
standard of care laboratory testing for breast cancer,"says lead author Kim M. Hirshfield, MD, Phd, breast medical oncologist at the Cancer Institute and assistant professor of medicine at Rutgers
Robert Wood Johnson Medical school. Utilizing the invasive breast cancer data set of 962 cases in The Cancer Genome Atlas
all breast cancers with alterations in the CDH1 gene (that gives instructions to make a protein that causes cancer cells to stick to one another
Tumors were evaluated by a pathologist at the microscopic level to classify them as either classic or pleomorphic lobular breast cancer.
An additional 16 cases from the Cancer Institute were evaluated using an advanced form of tumor DNA sequencing at RUCDR.
Of 116 eligible breast cancers from The Cancer Genome Atlas 86 were invasive lobular breast cancer. Of that number, 21 cases were found to be the pleomorphic type.
There were no significant differences in the frequency of the other gene alterations examined between the two types of cancer.
With that, investigators say the alterations in the ERBB2 gene strongly associate with pleomorphic lobular breast cancer but not the classic form of the disease.
Data from the additional 16 cases from the Cancer Institute validate the findings observed on breast cancers from The Cancer Genome Atlas."
"In identifying a specific abnormality in a patient's cancer instead of the overall organ where it first presented,
the opportunity exists to provide tailored therapies for patients,"notes Lorna Rodriguez, MD, Phd, director of the precision medicine initiative at the Cancer Institute and professor of obstetrics, gynecology and reproductive sciences
It is our aim at Rutgers Cancer Institute of New jersey to build upon this work,"notes senior author of the work, Shridar Ganesan, MD, Phd, associate director for translational science at the Cancer Institute
When a dental lesion appears, the dormant stem cells in the pulp awaken and try to repair the tooth by an unknown process.
two neurotransmitters that are essential to the body (see schema on page 2). The presence of these receptors on the surface of these stem cells indicated that they had the ability to respond to the presence of dopamine and serotonin in the event of a lesion.
activated by the dental lesion, are responsible for releasing a large quantity of serotonin and dopamine. Once released, these neurotransmitters then recruit the stem cells to repair the tooth by binding to their receptors (see schema on page 2). The research team was able to confirm this result by observing that dental repair was absent in rats with modified platelets that do not produce serotonin or dopamine,
and tricalcium phosphate-based biomaterials to repair the tooth and fill lesions. Our results lead us to imagine unprecedented therapeutic strategies aimed at mobilising the resident pulpal stem cells
#Researchers discover new drugs to combat the root cause of multiple sclerosis At the pathological level,
MS is a disease in which the immune system attacks the protective myelin sheath, a type of insulation that covers nerves,
slowing the progression of the disease. Our research is focused on trying to repair the brain itself,
to stop the disease rather than slow it, "said Robert Miller, Ph d.,co-author of the study and senior associate dean for research, Vivian Gill Distinguished Research Professor,
#Researchers develop Ebola treatment effective 3 days after infection The study results, in the April 22 edition of Nature Journal, demonstrated that the treatment is the first to be shown effective against the new Makona outbreak strain of Ebola in animals that were infected with the virus
and exhibited symptoms of the disease. The treatment uses a sequence specific short strand of RNA, known as sirna,
"We were able to protect all of our nonhuman primates against a lethal Makona Ebola infection
when treatment began three days following infection. At this point, those infected showed clinical signs of disease
and had detectable levels of virus in their blood.""Although all infected animals showed evidence of advanced disease,
those receiving treatment had milder symptoms and recovered fully. The untreated controls succumbed to the disease on days eight and nine,
which is reported similar to that in the field after patients begin showing symptoms of Ebola. This treatment also protected against liver
and kidney dysfunction and blood disorders that occur during an Ebola infection. These results indicate that the treatment may confer protective benefits that go beyond improving survival rates and effective control of virus levels in the body."
Phd, uncovered the critical role in pain processing of a gene associated with a rare disease.
Mutations in this gene also cause a rare human disease called the Nail-patella syndrome (NPS
and promise to be a powerful approach for many human diseases which don't yet have an effective treatment.
"Prof Shirley Hodgson, Professor of Cancer Genetics, St george's University of London, said:""I think that this is a significant departure from currently accepted research practice.
and you are trying to figure out the body's immune response to a particular pathogen, for example,
Then, combining that tissue-specific functional signal with the relevant disease's DNA-based genome-wide association studies (GWAS),
and diseases that would otherwise be undetectable. The resulting technique, which they called a'network-guided association study,
and identify genes underlying complex human diseases. And because the technique is driven completely data Netwas avoids bias toward better-studied genes
The paper goes on to describe functional gene disruptions for diseases such as hypertension, diabetes and obesity.
Many human cell types important to disease cannot be studied by traditional direct experimentation, so the ability to instead work with these rich datasets was a critical workaround."
and in many other disease-relevant tissues and cell types.""These findings have important implications for our understanding of normal gene function,
and the pathways that they uncover to understand drug action and side effects in the context of specific disease-relevant tissues,
and analyze data from genetic studies to find genes that cause disease. Aaron K. Wong, a data scientist at SCDA and formerly a graduate student in the computer science department at Princeton, led the way in creating GIANT."
"For example, with GIANT, researchers studying Parkinson's disease can search the substantia nigra network, which represents the brain region affected by Parkinson's,
and pathways involved in the disease.""Wong is one of three co-first authors of the paper.
polymer solutions were spun in an electrical field to form very fine threads and wound onto a spool."
"We did not find any aneurysms, thromboses or inflammation. Endogenous cells had colonized the vascular prostheses
and Strabismus (AAPOS) describes the effectiveness of a new computer-based vision-screening test, the Jaeb Visual acuity Screener (JVAS),
who then received a complete eye examination by an optometrist, which served as the study gold standard.
The examining optometrist was kept unaware of the initial JVAS vision screening results. No children who already wore glasses,
had been treated for amblyopia, or had undergone ocular surgery were included in the screening. The average screening time was 84 seconds, with a range of 23 to 357 seconds across all age groups.
Of the 65 children failing the gold standard examination, 86%failed for reduced visual acuity (56), 35%for hyperopia (23), 23%for astigmatism (15), 11%for anisometropia (7), 9%for myopia (6),
and 5%for strabismus (3), with some patients failing the gold standard for more than one reason.
For the 56 children with reduced visual acuity, the primary cause assigned hierarchically was uncorrected refractive error in 31 of 56 (55%),unilateral amblyopia in 7 (13%),bilateral amblyopia in 8 (14%
could allow biomedical engineers to identify appropriate binding sites for drugs used to treat cancer and other diseases.
In that case, jumping to the conclusion that the fruit was to blame for a bout of illness might help the animal steer clear of the same danger in the future.
for example, you might blame a new food you tried for an illness when in fact it was harmless,
and effect might lie at the heart of some psychiatric disorders that involve delusional thinking, such as schizophrenia."
The device is intended for use in remote laboratory settings to diagnose various types of cancers and nervous system disorders
as well as detect drug resistance in infectious diseases. To use the camera it is necessary to first isolate
Ozcan's group next plans to test their device in the field to detect the presence of malaria-related drug resistance e
#Uncovering new functions of a gene implicated in cancer growth opens new therapeutic possibilities Two decades ago,
was also present in cancer patients and contributing to tumor progression. The present study reveals another way that Id1 works, hijacking a normal pathway in immune cell development and interfering with the entire immune system, starting in the bone marrow.
Without competent immune cells, the body can't fight off tumors, and instead, cancer is allowed to grow,
spread and thrive.""Targeting Id1 offers the potential to restore overall immune function, "said senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a professor of pediatrics in the Department of Pediatrics at Weill Cornell Medical College."
"When the immune system is functioning, treatment options are more plentiful. Given the increased incidence and death rates tied to advanced stage metastatic cancers,
there is also an increased urgency to understand how pro-metastatic, immunosuppressive mechanisms, like those driven by Id1,
"The investigators discovered that a tumor-secreted protein called transforming growth factor beta (TGF? promotes the activation of Id1.
and allowing cancer to grow and spread unabated.""Normally, the bone marrow produces, among other immune cell types, dendritic cells,
and growth of tumors,"said first author Dr. Marianna Papaspyridonos, who was a Fulbright Cancer Research Fellow at Cornell University in Dr. Lyden's lab."But when TGF?
is released by the tumor and Id1 is upregulated, the normal generation of dendritic cells is interrupted,
and instead another subset of immune cells, which suppresses the immune system, is formed.""Those immune cells, called myeloid-derived suppressor cells,
allow cancer to more readily grow and spread. The researchers validated this finding in advanced melanoma patients,
who have increased TGF? plasma levels and higher levels of Id1 in myeloid peripheral blood cells. Targeting Id1 might provide a three-pronged therapeutic approach,
which would first reduce the metastatic potential of the tumor itself, then reduce the tumor's ability to form new blood vessels, a process called vasculogenesis,
and finally restore the patient's systemic immune function.""With this approach, immune cells will recognize a tumor as foreign and attack it,
"said Dr. Lyden, who also has appointments in the Sandra and Edward Meyer Cancer Center and the Gale and Ira Drukier Institute for Children's Health at Weill Cornell Medical College."
"This will improve vaccine development, lead to better treatment outcomes and ultimately benefit cancer patients
#Can photosynthesis be measured over large areas? Scientists find a way"Plant photosynthesis is a fundamental process that drives all ecosystem functions.
Viruses responsible for 50 percent of gastroenteritis Noroviruses, a group of viruses responsible for over 50%of global gastroenteritis cases, can spread by air up to several meters from an infected person
The discovery, details of which are presented in the latest issue of Clinical Infectious diseases, suggests that measures applied in hospitals during gastroenteritis outbreaks may be insufficient to effectively contain this kind of infection.
The team led by Caroline Duchaine, professor at Université Laval's Faculty of science and Engineering and researcher at the Québec Heart and Lung Institute (IUCPQ) Research Centre
and long-term care facilities affected by gastroenteritis outbreaks. Researchers gathered air samples at a distance of 1 meter from patients, at the doors to their rooms,
The viruses were detected in 54%of the rooms housing patients with gastroenteritis, 38%of the hallways leading to their rooms,
A dose of 20 norovirus particles is usually enough to cause gastroenteritis. According to Professor Duchaine
this previously unknown mode of norovirus propagation could explain why gastroenteritis outbreaks are so hard to contain:"
Use of mobile air filtration units or the wearing of respiratory protection around patients with gastroenteritis are measures worth testing. i
However, if cells are exposed to oxidative stress, SIRT1 ubiquitination promotes cell death. These results are important
"SIRT1 is known to be expressed abnormally in a variety of cancers and might be a good target for therapy.
Ubiquitin-proteasome inhibitors have already been used successfully in cancer therapy and clinical trials. Therefore, this research might provide molecular bases
and insights for developing additional therapeutic strategies in the future,"explained Ed Seto, Ph d.,senior member of the Cancer Biology and Evolution Program at Moffitt t
The new work also reveals more about certain cancers that arise when these processes go astray, for example,
"Both the Wnt and Activin signaling processes operate differently in cancer, compared to stem cells.
The aberrant behavior of the Activin process, meanwhile, is tied to the metastasis of many cancers."
because these would have strong anticancer activity for many tumor types, "says Estar#s ."Because the environment of stem cells and cancer cells are quite distinct,
and regulation that we have defined in stem cells operates in the cells of a tumor. u
NONO helps to mend the damage The study appeared as advanced online publication on Oncogene, a journal in cancer research from the Nature Publishing Group.
a multifunctional protein involved in melanoma development and progression, in the cellular response to UV radiations.
or transmitted to daughter cells during mitosis. Luigi Alfano, Phd of the National Cancer Institute of Naples-Pascale Foundation-CROM-Cancer Research center of Mercogliano,
"Considering that many studies are identifying NONO alterations in cancer, our findings will likely help to shed light on the molecular mechanisms of tumorigenesis, especially in tumour types like melanoma, in which exposure to UV radiations plays such a prominent part.
Our work also provides the preclinical framework supporting the development of new agents targeting NONO that could be used to sensitize cancer cells to a variety of drugs that cause DNA damage,
such as common chemotherapy agents,"states Francesca Pentimalli Phd from the National Cancer Institute of Naples co-corresponding of the study with Antonio Giordano,
Director of the Sbarro Institute for Cancer Research and Molecular Medicine, at Temple University, Philadelphia a
because they often have latent ischaemic heart disease which reduces blood flow to the heart. Latent means they don't have any clinical signs
or symptoms, making it very difficult to predict a future heart attack.""He continued:""Ischaemic heart disease should be diagnosed at an early stage
so that preventive therapies can be given. But exercise stress testing is inappropriate for diagnosis in hemodialysis patients who have multiple complications including muscle weakness, osteoporosis and peripheral arterial disease."
"The current study investigated the ability of 3 methods, alone or in combination, to predict the risk of sudden cardiac death in hemodialysis patients.
which could be caused by latent ischaemic heart disease and may lead to fatal cardiac events.""He added:"
"An abnormal Q wave indicates the presence of previous myocardial infarction or serious myocardial injury responsible for low cardiac output, heart failure and/or potentially fatal arrhythmias.
High C reactive-protein protein levels reflect any active inflammatory reactions such as infection or atherosclerosis.""Dr Hashimoto continued:"
Abnormal BMIPP identifies specific myocardial injury which could be an effective therapeutic target for preventing sudden cardiac death."
Cardiac function assessment for heart failure, coronary angiography for ischaemic heart disease and Holter ECG monitoring for lethal arrhythmias can identify the type of myocardial injury
It detects scar tissue formed after the heart muscle is damaged by a heart attack. 3. C reactive-protein protein is a nonspecific test used to detect inflammation in the body.
because they often have latent ischaemic heart disease which reduces blood flow to the heart. Latent means they don't have any clinical signs
or symptoms, making it very difficult to predict a future heart attack.""He continued:""Ischaemic heart disease should be diagnosed at an early stage
so that preventive therapies can be given. But exercise stress testing is inappropriate for diagnosis in hemodialysis patients who have multiple complications including muscle weakness, osteoporosis and peripheral arterial disease."
"The current study investigated the ability of 3 methods, alone or in combination, to predict the risk of sudden cardiac death in hemodialysis patients.
which could be caused by latent ischaemic heart disease and may lead to fatal cardiac events.""He added:"
"An abnormal Q wave indicates the presence of previous myocardial infarction or serious myocardial injury responsible for low cardiac output, heart failure and/or potentially fatal arrhythmias.
High C reactive-protein protein levels reflect any active inflammatory reactions such as infection or atherosclerosis.""Dr Hashimoto continued:"
Abnormal BMIPP identifies specific myocardial injury which could be an effective therapeutic target for preventing sudden cardiac death."
Cardiac function assessment for heart failure, coronary angiography for ischaemic heart disease and Holter ECG monitoring for lethal arrhythmias can identify the type of myocardial injury
#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,
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,
"We could completely inhibit tumor growth after just one dose of the cancer vaccine in the animal model,
. 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,
"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.
a cell surface hormone receptor that is overexpressed in the tumor cells of 15 to 30 percent of breast cancer patients.
"But these vaccines have mostly not been very potent because of inefficient vaccine delivery, a poor immune response at the site of the tumor,
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."
"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,
"Hypertension can lead to severe health issues such as heart attacks, kidney failure, organ damage, and weakened or ruptured blood vessels.
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.
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."
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.
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