#Physiologists uncover a new code at the heart of biology UT Southwestern physiologists trying to understand the genetic code have found a previously unknown code that helps explain which protein should be created to form a particular type of cell.
This can have important implications for identifying human disease-causing mutations because this study indicates that a mutation does not have to change amino acid identity to cause a disease.
In fact, most mutations in human DNA do not result in amino acid change.""Therefore, our study indicates that the new"code"--the speed limit of assembly--within the genetic code can dictate the ultimate function of a given protein,
one cancerous cell breaks off from a tumor, slips into the bloodstream and quickly lodges elsewhere in the body.
These colonizers may bloom into deadly metastatic cancer right away or lie dormant for years, only to trigger a recurrence decades after the primary tumor is removed.
Metastases cause the vast majority of cancer deaths, but their tiny seeds are so difficult to track that few researchers have managed to study them.
Now, scientists from UC San francisco describe capturing and studying individual metastatic cells from human breast cancer tumors implanted into mice as the cells escaped into the blood stream
and began to form tumors elsewhere in the body. The researchers discovered that genetic programs expressed in these cells were quite distinct from the primary tumors in
which they originated and included genes typically expressed in mammary stem cells. The findings, published online Sept. 23,2015 in Nature, could change the way researchers think about how cancer spreads
and suggest new drugs to track down and disable its deadly seeds. For the most part, modern cancer drugs ignore differences between primary
and metastatic tumors, said Zena Werb, Phd, professor and vice-chair of anatomy at UCSF, and a senior author on the new study."
"We test drugs for their ability to make primary tumors shrink, but most just don't work on metastases,
"Patients have their original tumor treated or removed, but then the cancer comes back 20,30, 40 years later because there were just a few metastatic cells sitting around."
"Catching metastatic cancer cells in the act No one really knows how dormant metastatic cells can survive incognito for decades,
"It's a big black box in the cancer field--mostly because it's very difficult to study,
only about 7 percent of all breast cancer funding goes to studying metastatic cancer, despite the fact that it causes virtually all breast cancer deaths.
Previous work by Werb's group had found a subset of cells at the edges of breast cancer tumors that seemed primed to metastasize.
and with proteins in the surrounding tumor microenvironment seemed to turn on genetic programs akin to those of mammary stem cells--the cells that allow breasts to form during puberty
These genes for self-replication could make these cells particularly apt to generate new tumors elsewhere in the body.
which involves transplanting human tumor cells into mice. Against the backdrop of healthy mouse tissue, rogue metastatic cells from the human tumor stick out like flares.
The researchers developed a new method using flow cytometry that let them capture individual human metastatic cancer cells traveling through the mouse's blood
the cancer cells'gene activity looked much like that of the primary tumor that had been transplanted into the mice,
In contrast, early-stage metastases and cancer cells traveling through the blood expressed genes typically active in mammary stem cells and quite distinct from primary tumor cells.
Remarkably, the same signature pattern of gene activity was found in metastatic cells in mice whose tumors came from genetically and clinically diverse human patients.
In other words, the genetic program that makes a cell metastatic did not depend on the genetics of its tumor of origin--suggesting that new techniques might allow researchers to find
Since metastatic cells that were beginning to differentiate into secondary tumors showed high expression of genes cmyc and CDK2, the researchers treated 24 PDX mice with dinaciclib,
Whereas 44 percent of control mice (11 of 25) developed secondary tumors within four weeks, researchers could only find metastatic cells in one drug-treated mouse (4 percent.
was that the drug managed to nearly eliminate metastases without shrinking the primary tumor.""If this drug had only been tested on primary tumors,
we would have said it doesn't work, "she said.""This tells us you actually have to look at metastases
"Preventing metastatic cells from invading other parts of the body has been a priority for cancer researchers for many years,
by the time you've detected the tumor, that horse is either already out of the barn
and while many of these are beneficial, some can cause disease. For example some reports have linked Crohn's disease to the presence of certain strains of E coli."
"We'd like to be able to remove specific members of the bacterial population and see what their function is in the microbiome,
and gastrointestinal infections, including pneumonia, sepsis, gastritis, and Legionnaires'disease. One advantage of the engineered phages is that unlike many antibiotics,
they are very specific in their targets.""Antibiotics can kill off a lot of the good flora in your gut,
"We aim to create effective and narrow-spectrum methods for targeting pathogens.""Lu and his colleagues are now designing phages that can target other strains of harmful bacteria,
as well as treating human disease. Another advantage of this approach is that all of the phages are based on an identical genetic scaffold,
including in cancer research, "said Levi Garraway, an institute member of the Broad Institute, and the inaugural director of the Joint Center for Cancer Precision Medicine at the Dana-Farber Cancer Institute, Brigham and Women's Hospital,
and the Broad Institute. Garraway was involved not in the research. Zhang, Broad Institute, and MIT plan to share the Cpf1 system widely.
#Cabozantinib improves survival in patients with advanced kidney cancer: Results from the METEOR trial Patients with advanced kidney cancer live for nearly twice as long without their disease progressing
if they are treated with cabozantinib, a drug that inhibits the action of tyrosine kinases--enzymes that function as an"on
"or"off"switch in many cellular processes, including cancer. In the second of two late-breaking presentations of research that is predicted to change the way kidney cancer patients are treated,
Professor Toni Choueiri will tell the presidential session of the 2015 European Cancer Congress 1,
about results from the first 375 patients out of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus,
the current standard treatment for the disease. Analysis of results in July 2015 showed that the estimated median (average) progression-free survival time for patients with advanced clear cell kidney cancer,
randomised to receive cabozantinib, was 7. 4 months, while it was 3. 8 months for those receiving everolimus.
who is Associate professor of Medicine at Harvard Medical school and Clinical Director and Kidney Cancer Center Director at The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute,
since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR)."
"Although treatment with VEGFR-targeted drugs has been very effective in the first line of therapy for patients with advanced kidney cancer,
This has resulted in a significant reduction in the rate of disease progression or death in the cabozantinib arm as compared with the everolimus arm.
Regaining tumour control after prior targeted therapy may reduce symptoms related to kidney cancer and eventually help patients live longer."
Overall, these results should give new hope to patients diagnosed with advanced kidney cancer as cabozantinib may become a new treatment option."
"Clear cell kidney cancer (or renal cell carcinoma) is one of the commonest kidney cancers--70-80%of kidney cancer patients have this type.
81%of patients with stage I disease, in which the tumour is confined to the kidney,
with only around eight percent of patients with stage IV disease surviving for five years.
Their disease had to have progressed within six months of receiving prior treatment with VEGFR tyrosine kinase inhibitor (TKI) therapy.
%shortness of breath (3. 7%)and pneumonia (3. 7%).Prof Choueiri said:""The METEOR results are important from a clinical and scientific point of view.
or resistance to standard therapies is critical for improving long-term outcome for our patients with advanced kidney cancer.
Further studies include a randomised phase II study of cabozantinib versus standard of care with sunitinib as a first treatment for advanced renal cell cancer.
and an early stage clinical trial combining cabozantinib with immune checkpoint inhibitors has been initiated in urological cancers,
including patients with kidney cancer.""The trial has stopped recruiting patients and researchers are hoping that cabozantinib may become available to patients with advanced kidney cancer some time in 2016.
In the USA, the Food and Drug Administration (FDA) has designated it as a breakthrough therapy,
"I am excited over the advances in treatment of renal cell carcinoma that we are at present.
who will be reporting results from the Checkmate 025 randomised phase III trial of nivolumab versus everolimus in advanced kidney cancer r
and this may lead to congestive heart failure or it may worsen an existing heart failure. Pioneered by Associate professor Leo Hwa Liang from the Department of Biomedical engineering at NUS'Faculty of engineering
or are suffering from multiple chronic diseases are not suitable for the treatment. Although current mitral valve interventions delivered via a small incision through the skin could be a viable alternative treatment
"Cone transplant represents a therapeutic solution for retinal pathologies caused by the degeneration of photoreceptor cells,
offering hope that treatments may be developed for currently non-curable degenerative diseases, like Stargardt disease and ARMD."
ARMD is in fact the greatest cause of blindness amongst people over the age of 50
Beyond the clinical applications, Professor Bernier's findings could enable the modelling of human retinal degenerative diseases through the use of induced pluripotent stem cells,
#Possible new treatment for bladder cancer using a mycobacterium Universitat Autònoma de Barcelona researchers have found a mycobacterium that is more effective in treating superficial bladder cancer
and does not cause infections, unlike those used up to now. Mycobacteria are the only bacteria used in cancer treatment.
The administration of the bacterium Mycobacterium bovis (BCG), is the current treatment for superficial bladder cancer.
It is inserted directly into the bladder through a catheter. BCG prevents new tumours from appearing,
the most serious being BCG infections that need to be treated with antituberculous drugs. A study on the characteristics of a wide group of mycobacteria begun seven years ago by the Mycobacteria Research Group
Preclinical studies using mouse models of bladder cancer have demonstrated the efficacy of the mycobacterium M. brumae in the treatment of this disease.
presenting no risk of causing infections, which means it would have fewer adverse side effects on patients than BCG.
which is given significant that in the last few years BCG production problems have led to supply issues for certain bladder cancer patients."
"Our results suggest that Micobacterium brumae is an ideal candidate to replace the current BCG treatment for superficial bladder cancer,
The study, published in the journal European Urology Focus, was conducted in collaboration with Dr Rosa M. Rabanal of the Murine and Comparative Pathology Unit, Department of Animal Medicine and Surgery, UAB,
and with the group Bacterial Infections and Antimicrobial Therapies led by Dr Eduard Torrents, of the Institute for Bioengineering of Catalonia (IBEC) I
#New test predicts teens'future risk of heart disease Risk for cardiovascular disease, currently running rampant in the United states,
The test accounts for many risk factors for the deadly disease and has the potential to be adapted by physicians nationwide to assess teenagers'future risk
Risk Factors for Cardiovascular disease Approximately 610,000 people die from heart disease every year in the United states--that's one of every four deaths.
Cardiovascular disease has predominantly modifiable risk factors meaning that the disease is entirely preventable. These modifiable risk factors include high blood pressure, high cholesterol, obesity, physical inactivity, diabetes, unhealthy diets and smoking.
The only risk factor unable to be changed is genetic predisposition. The Role of Metabolic syndrome The new diagnostic test has been developed by a team that included Mark Deboer, MD, of the University of Virginia Children's Hospital's Department of Pediatrics,
and Matthew Gurka, Phd, of West virginia University's School of Public health. The test relies on an evaluation of metabolic syndrome,
a conglomeration of conditions including increased blood pressure, high levels of blood sugar, excessive body fat around the abdomen and waist,
and abnormal cholesterol levels that together increase the risk of cardiovascular disease. It takes into account variables specific both to race and gender."
"The way that we normally diagnose metabolic syndrome appears to have some racial discrepancies where African-american individuals are diagnosed not with metabolic syndrome at a very high rate
and yet they are at very high risk for developing type 2 diabetes and CVD cardiovascular disease,
so Dr. Gurka and I formulated a metabolic syndrome severity score that is specific to sex and ethnicity,
"Deboer said. In creating the test, Deboer and Gurka examined metabolic severity scores from children in the 1970s that assessed body mass index (BMI), systolic blood pressure, fasting triglycerides, HDL cholesterol and fasting glucose.
"The current study was targeted at using that metabolic syndrome severity score on data from individuals who were children in the'70s to see
if it correlated with their risk on developing CVD and type 2 diabetes later in life,
and we found that there was a high correlation between the metabolic severity score for those children and for their later development of cardiovascular disease and diabetes,
The Use of the Test The test is innovative in that it is able to assess changes in metabolic syndrome severity in a person over time
or does not have metabolic syndrome, but the new test is able to create a scale,
"We are hopeful that this score can be used to assess the baseline risk for adolescents regarding metabolic syndrome
and their risk for future disease and use it as a motivator for individuals to try to change their risk
or get medication to reduce their metabolic syndrome severity and their future risk for disease, "Deboer said d
#Groundbreaking computer program diagnoses cancer in two days In by far the majority of cancer cases, the doctor can quickly identify the source of the disease, for example cancer of the liver, lungs, etc.
However, in about one in 20 cases, the doctor can confirm that the patient has cancer
and attempts to locate the origin of the cancer before starting any treatment. Now, researchers at DTU Systems Biology have combined genetics with computer science
which--on the basis of a biopsy from a metastasis--can with 85 per cent certainty identify the source of the disease
Each year, about 35,000 people are diagnosed with cancer in Denmark, and many of them face the prospect of a long wait until the cancer has been diagnosed and its source located.
However, even after very extensive tests, there will still be 2-3 per cent of patients where it has not been possible to find the origin of the cancer.
In such cases, the patient will be treated with a cocktail of chemotherapy instead of a more appropriately targeted treatment
are based on analyses of DNA mutations in cancer tissue samples from patients with metastasized cancer,
i e. cancer which has spread. The pattern of mutations is analysed in a computer program which has been trained to find possible primary tumour localizations.
whether an individual cancer patient will benefit from a specific type of medicine. This is a very effective method,
and it is becoming increasingly common to conduct such sequencing for cancer patients. Associate professor Aron Eklund from DTU Systems Biology explains:"
"We are pleased very that we can now use the same sequencing data together with our new algorithms to provide a much faster diagnosis for cancer cases that are difficult to diagnose,
and thus also as an effective and easy way of monitoring people who are at risk of developing cancer.
Tumor tracer A diagnostic method for determining the primary site of the cancer. The method combines genetics and computer science,
and on this basis provide a number of possible scenarios for where the cancer may have developed
Ultimately, it could be used in the early diagnosis of brain tumours or Alzheimer's disease. This work is published in PNAS.
Many diseases involve structural changes in tissues which are reflected in a change in their mechanical properties, such as elasticity.
"Alzheimer's disease, epilepsy, multiple sclerosis and hydrocephalus involve changes in the stiffness of the brain tissues. This new technique allows their detection,
such as for analysing the development of neurodegenerative processes, the impact of a lesion from a trauma or tumour, response to treatment, etc e
'Complex array of mutations found in rare, aggressive leukemia Sezary syndrome (SS), an aggressive leukemia of mature T cells, is complicated more at a molecular level than ever suspected, according to investigators from the Perelman School of medicine at the University of Pennsylvania.
With a poor prognosis and limited options for targeted therapies, fighting SS needs new treatment approaches.
The team's results uncover a previously unknown, complex genomic landscape of this cancer, which can be used to design new personalized drug regimens for SS patients based on their unique genetic makeup.
Sezary syndrome is a rare condition: Its incidence is estimated to be about 0. 3-2 cases per 100,000 in the United states each year,
complementary gene sequencing approaches to look for mutations in tumor cells from SS patients: whole-genome sequencing in six subjects,
drugs that are approved currently for treatment of other hematologic cancers such as polycythemia vera and myelofibrosis."
"The Penn team, in collaboration with Alain Rook, MD, director of the Cutaneous T-cell Lymphoma Program and a professor of Dermatology, aims to develop a molecular taxonomy for mutations in SS patients.
From this, they will also be able to identify distinct subsets of the disease to stratify patients for precision therapy based on their unique mutations and the inhibitors available for those mutations s
#Scientists pave way for diamonds to trace early cancers Physicists from the University of Sydney have devised a way to use diamonds to identify cancerous tumours before they become life threatening.
synthetic version of the precious gem can light up early-stage cancers in nontoxic, noninvasive Magnetic resonance imaging (MRI) scans.
Targeting cancers with tailored chemicals is not new but scientists struggle to detect where these chemicals go since,
if a treatment has been taken up by a cancer. Led by Professor David Reilly from the School of Physics
researchers from the University investigated how nanoscale diamonds could help identify cancers in their earliest stages."
"By attaching hyperpolarised diamonds to molecules targeting cancers the technique can allow tracking of the molecules'movement in the body,
and target cancers long before they become life-threatening, "says Professor Reilly. The next stage of the team's work involves working with medical researchers to test the new technology on animals.
#3d image of cancer protein aids quest for new treatments Scientists at the Walter and Eliza Hall Institute have created the first three-dimensional image of a key protein known to be involved in the development of blood and other cancers.
The discovery showed the protein, called Trib1, plays a vital role in controlling how and when other proteins are degraded,
The finding could be used to develop new drugs to treat cancers such as leukaemia, caused by malfunctioning of the Trib1 protein.
causing a type of blood cancer called acute myeloid leukemia (AML). Institute researchers Dr James Murphy and Dr Isabelle Lucet, in collaboration with Dr Peter Mace from the University of Otago, New zealand, characterised the human Tribbles protein Trib1.
and can lead to diseases such as cancer.""Using the Australian Synchrotron, Dr Mace, Dr Murphy and colleagues were able to obtain detailed three-dimensional images of Trib1."
which will provide critical clues for developing drugs that target Trib1 to treat cancers.""Lead investigator Dr Mace said Trib1 acted as a scaffold to bring many proteins together,
which causes a loss of proteins that would normally inhibit cancer. Understanding the structure of Trib1 provides critical clues about how we could block Tribbles for the treatment of AML."
"We are excited about pursing this research for the treatment and eradication of HIV infections.""The two therapies were tested together in laboratory experiments using human immune cells
Gelbard, director of UR's Center for Neural development and Disease, developed URMC-099 to treat HIV-associated neurocognitive disorders or HAND,
reduce side effects and help people manage the disease, because they won't have to think about taking medication every day
the result is a potentially fatal arrhythmia. Now, a team of researchers from Oxford and Stony Brook universities has found a way to precisely control these waves--using light.
'When there is scar tissue in the heart or fibrosis, this can cause part of the wave to slow down.
especially mutations, has become critically important for the detection of diseases and design of therapies to treat them.
"In one of many successful tests, the lab designed molecules to detect mutation sequences in historic biopsy samples preserved in wax from cancer patients.
One of the researchers'goals is to design noninvasive cancer diagnostics that detect DNA biomarkers in blood samples for early screening and early recurrence detection.
and apply it to cancer detection n
#New approach toward a broad spectrum malaria vaccine Malaria affects millions of people worldwide. Plasmodium falciparum enolase participates in parasite invasion of host red blood cells and mosquito midgut epithelium.
Anti-enolase antibodies interfere with the invasion, inhibiting parasite growth and transmission. A pentapeptide insert of parasite enolase, conserved in all Plasmodia species,
shows considerable protection against malaria when displayed on Archaeal gas vesicle nanoparticles. A vaccine based on this motif could confer protection against all malaria parasites.
In a recent breakthrough to combat malaria, a collaboration of Indian and American scientists have identified a malarial parasite protein that can be used to develop antibodies
The finding points towards developing a powerful malaria vaccine in the hope of eradicating this debilitating and often fatal disease.
Malaria takes a heavy toll on human lives. About half a million people die every year and several hundred million suffer from this disease across the globe.
To add to the disease burden, the malaria parasite is increasingly becoming resistant to commonly used antimalarial drugs.
Development of an antimalarial vaccine is an integral part of an effort to counter the socioeconomic burden of malaria.
Researchers in the malaria labs at Tata Institute of Fundamental Research (TIFR Mumbai, India, have identified now a five amino acid segment of a Plasmodium parasite protein that is normally involved in producing energy from glucose.
Work from Prof. Gotam Jarori's lab has shown earlier that this protein, enolase, is a protective antigen
Taking this a step further, in a recently published paper in the Malaria Journal, they have shown that a small part of this protein,
Interestingly, a subsequent challenge with a lethal strain of mouse malaria parasite in these vaccinated animals showed considerable protection against malaria.
and this work is a significant step forward towards a new malaria vaccine.""This study is a significant advance in the field,
"The small segment of five amino acids that forms a protective epitope is present in all human malaria causing species of Plasmodium and hence,
Efforts are focused now at developing this into an effective vaccine against malaria a
#Turning up the heat: Holey metamaterials enhance thermal energy harvesting It's estimated that the U s. fails to use more than half of the energy it generates--mostly
An abnormally high or low white blood count, for instance, might indicate a bone marrow pathology or AIDS.
The rupturing of white blood cells might be the sign of an underlying microbial or viral infection.
Strangely shaped cells often indicate cancer. While this old, simple technique may seem a quaint throwback in the age of high-technology health care tools like genetic sequencing
#Gene could hold key to treating Parkinson's disease Researchers at King's college London have identified a new gene linked to nerve function,
which could provide a treatment target for'switching off'the gene in people with neurodegenerative diseases such as Parkinson's disease.
Parkinson's disease affects approximately 7-10 million people worldwide and is characterized by progressive loss of motor function, psychiatric symptoms and cognitive impairment.
Current treatments for Parkinson's only treat symptoms of the disease rather than its underlying causes,
play an important role in a number of diseases that affect the nervous system, including Parkinson's.
nerve function in flies with Parkinson's disease was restored. By deactivating the HIFALPHA gene the early failure of nerve cells caused by mitochondrial damage was prevented.
An identical effect was observed in flies with Leigh syndrome, a rare neurological disorder caused by a severe mitochondrial defect,
'Like their human counterparts flies with Parkinson's disease progressively lose motor function, which includes a negative impact on their ability to climb.
"Although we are currently looking at neurodegenerative disease, there is potential for the technology to be expanded to psychiatric diseases, chronic pain,
seizure disorders and many other conditions affecting the brain and nervous system down the road.""Using nasal mucosal grafting,
a therapeutic protein in testing for treating Parkinson's disease, to the brains of mice. They showed through behavioral
and histological data capture that their delivery method was equivalent to direct injection of GDNF--the current gold standard for delivering this drug in Parkinson's disease despite its traumatic nature and high complication rates--in diffusing drugs to the brain.
because the therapy has been shown to delay and even reverse disease progression of Parkinson's disease in preclinical models.
"Brain diseases are notoriously difficult to treat due to the natural protections the body builds against intrusion,
and we look forward to the next stage of research to further test its utility in people with Parkinson's disease."
ENT surgeons commonly use endoscopic approaches to remove brain tumors through the nose by making a window through the blood-brain barrier to access the brain.
with the nasal lining protecting the brain from infection just as the blood brain barrier has done. Dr. Bleier saw an opportunity to apply these techniques to the widespread clinical dilemma of delivering drugs across the barrier to the brain and central nervous system.
"We see this expanding beyond Parkinson's disease, as there are multiple diseases of the brain that do not have good therapeutic options,
"Dr. Bleier said.""It is a platform that opens doors for new discovery and could enable drug development for an underserved population
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