#Researchers find protein that may signal more aggressive prostate cancers Biomarkers in the body are analogous to the warning lights in cars that signal something might need repairing.
"In the context of prostate cancer) there's a big interest in trying to find biomarkers to discriminate between aggressive and nonaggressive disease,
Prostate cancer can grow so slowly the carrier dies of natural causes before the cancer spreads,
and could provide a potential new drug target for prostate cancer, "Franceschi said.""It could also be a potential biomarker to discriminate between fast and slow growing tumors."
"The U-M researchers made the discovery in a roundabout way, said Franceschi, whose research lab mainly studies bone formation, not cancer."
"We discovered this regulatory mechanism in bone cells, but subsequently found it was also operative in prostate cancer cells,
"This is the first paper the lab has published on cancer.""The idea is that adding a phosphate group, a process called phosphorylation, to the protein Runx2,
However, in prostate cancer cells, Runx2 triggered genes that fuel tumor growth and metastasis."It's unusual that a protein
whose function is to produce bone has this unusual function in prostate cancer, "Franceschi said.
and found that tumor growth was reduced. Franceschi's lab also collaborated with researchers in Italy to analyze tissue samples from 129 patients with prostate cancer.
They found little or no Runx2 phosphorylation in normal prostate, benign prostate or prostatitis, which suggests that Runx2 phosphorylation is associated closely with the more aggressive forms of prostate cancer.
The next step is to establish an actual cause-effect relationship between Runx2 phosphorylation and prostate cancer.
To do this they will compare prostate cancer formation in normal mice and mice lacking Runx2 in their prostates.
Worldwide, prostate cancer is the second-most common cancer in men, according to the World Cancer Research Fund International.
In the U s.,about 221,000 new cases of prostate cancer will be diagnosed in 2015 resulting in roughly 27,500 deaths s
#Hyper-stretchable elastic-composite energy harvester Scientists have developed a hyper-stretchable elastic-composite energy harvesting device called a nanogenerator.
A research team led by Professor Keon Jae Lee of the Department of Materials science and engineering at the Korea Advanced Institute of Science
For example, wearable/biomedical devices and electronic skins (e skins) should stretch to conform to arbitrarily curved surfaces and moving body parts such as joints, diaphragms, and tendons.
These noteworthy results were achieved by the non-destructive stress-relaxation ability of the unique electrodes as well as the good piezoelectricity of the device components.
It can open avenues for power supplies in universal wearable and biomedical applications as well as self-powered ultra-stretchable electronics
low-cost molecular tumor diagnosis A device developed by Massachusetts General Hospital investigators may bring rapid,
accurate molecular diagnosis of tumors and other diseases to locations lacking the latest medical technology.
"The global burden of cancer, limited access to prompt pathology services in many regions and emerging cell profiling technologies increase the need for low-cost,
"says Cesar Castro, MD, of the MGH Cancer Center and Center for Systems Biology, co-lead author of the report."
"The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy,
supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators and patients;
"The device the team has developed--called the D3 (digital diffraction diagnosis) system--features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.
and the results rapidly returned to the point of Care for molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules
and are loaded into the D3 imaging module. After the image is recorded and data transmitted to the server,
A pilot test of the system with cancer cell lines detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling,
The investigators then conducted analysis of cervical biopsy samples from 25 women with abnormal PAP SMEARS--samples collected
along with those used for clinical diagnosis--using microbeads tagged with antibodies against three published markers of cervical cancer.
Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk or benign, with results matching those of conventional pathologic analysis
. D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate four patients
whose lymphoma diagnosis was confirmed by conventional pathology from another four with benign lymph node enlargement. Along with protein analyses, the system was enhanced to successfully detect DNA--in this instance from human papilloma virus--with great sensitivity.
and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings, "says Ralph Weissleder, MD, Phd, director of the MGH Center for Systems Biology (CSB) and co-senior author of the paper."
or high-risk cases that could help to offset delays caused by limited pathology services in those regions
and DNA markers of other disease catalysts, including infectious agents and allergens; 2) integrate the software with larger databases;
both in normal conditions and in situations of stress--like the body experiences following a bone marrow transplant.
the discovery opens new lines of inquiry about the Ash1l gene's potential role in cancers known to involve other members of the same gene family,
like leukemia, or those where Ash1l might be expressed highly or mutated.""It's vital to understand how the basic,
and an associate professor in the Division of Hematology-Oncology at the U-M Medical school.""Leukemia is a cancer of the body's blood-forming tissues,
so it's an obvious place that we plan to look at next. If we find that Ash1l plays a role,
Dysfunction of blood-forming stem cells is well known in illnesses like leukemia and bone marrow failure disorders.
and radiation used to treat cancer. The replacement of these cells through bone marrow transplantation is the only widely established therapy involving stem cells in human patients.
But even in the absence of disease, blood cells require constant replacement--most blood cells last anywhere from a few days to a few months,
depending on their type. Over more than five years, Maillard and his collaborators identified a previously unknown
The Ash1l (Absent, small or homeotic 1-like) gene is part of a family of genes that includes MLL1 (Mixed Lineage Leukemia 1),
a gene that is frequently mutated in patients who develop leukemia. The research found that both genes contribute to blood renewal;
Ash1l-deficient stem cells were unable to establish normal blood renewal after a bone marrow transplant.
After the U s. dropped atomic bombs on Hiroshima and Nagasaki, doctors noticed that radiation patients weren't able to generate new white blood cells to fend off infections.
Subsequent experiments on mice showed that bone marrow transplants from healthy animals into irradiated ones could renew their ability to make new blood cells.
including those whose blood stem cells are killed off by cancer treatments. But work continues in the laboratory setting."
#New biomarker for uterine cancer discovered Researchers at Uppsala University have, together with researchers from Turku and Bergen, discovered a new biomarker
which makes it possible to identify women with uterine cancer who have a high risk of recurrence.
The findings were published recently in the journal Gynecologic Oncology. Endometrial cancer of the uterus is the most common form of gynecologic cancer in Europe and North america.
The treatment primarily consists of removing the uterus and in some cases offering chemotherapy if the risk of recurrence is deemed high.
The current study looks at the amount of protein ASRGL1 present in the tumour cells in uterine cancer.
Turku and Bergen and is collected based on samples from 500 women who were diagnosed with uterine cancer between the years 1981 and 2007.
or partially lost ASRGL1 in the tumour cells had a much higher risk of the cancer recurring
and dying from the disease, while patients with sustained high levels of ASRGL1 had a much lower risk of recurrence.
'I view the results as a first step towards personal treatment of uterine cancer. Today, 10-15 per cent of the patients suffer recurrences,
and offer them more aggressive treatment after their operation increases',says Per-Henrik Edqvist, researcher at Uppsala University's Department of Immunology, Genetics and Pathology,
whether ASRGL1 also can be used for diagnosing tissue biopsies taken before the operation, to identify patients in need of more extensive surgery.'
'Our results are promising, but more research is needed before ASRGL1 can be accepted as a new diagnostic tool in healthcare.
since Swedish biotech company Atlas Antibodies has shown interest in commercialising our findings, 'says Per-Henrik Edqvist.
It was within The Human Protein Atlas project that the expression of the ASRGL1 protein was mapped first in the human body's normal tissues and in different forms of cancer.
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."
"Our studies have shown that the protein megalin is almost always detectable in malignant melanomas, while it is rarely found in the benign counterparts.
"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
and relapse or not from a malignant melanoma.""It is a new and interesting marker that no one has thought of before.
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 s
#Shape-shifting molecule tricks viruses into mutating themselves to death A newly developed spectroscopy method is helping to clarify the poorly understood molecular process by
But scientists have developed therapeutic antiviral agents for HIV Hepatitis C, and influenza using a strategy called lethal mutagenesis.
This strategy seeks to extinguish viruses by forcing their already high mutation rates above an intolerable threshold.
If viruses experience too many mutations, they can't properly manage their genetic material.""They can't replicate
Toxicology, and Biological engineering. Essigmann is cofounder of a pharmaceutical company that is developing mutagenic inhibitors of HIV."
"KP1212 is about 20 percent of the way toward being an ideal therapeutic mutagen. The hints given us by the spectroscopy guide us toward even better mutagenic molecules,
But together their research teams were able to fruitfully undertake one of the first 2d infrared spectroscopic studies of the therapeutic mechanism of an antiviral drug."
#Electronic micropump to deliver treatments deep within the brain Drugs constitute the most widely used approach for treating brain disorders.
Epilepsy is a typical example of a condition for which many drugs could not be commercialised because of their harmful effects,
During an epileptic seizure, the nerve cells in a specific area of the brain are activated suddenly in an excessive manner.
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,
by allowing very localised action, directly in the brain and without peripheral toxicity.""By combining electrodes,
such as those used to treat Parkinson's disease, with this micropump, it may be possible to use this technology to treat patients with epilepsy who are resistant to conventional treatments,
and those for whom the side-effects are too great, "explains Christophe Bernard, Inserm Research director. Based on these initial results, the researchers are now working to move on to an in vivo animal model
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 e
#Genetics overlap found between Alzheimer's disease, cardiovascular risk factors The findings are published in current online issue of Circulation."
"For many years we have known that high levels of cholesterol and high levels of inflammation are associated with increased risks for Alzheimer's disease,
"said study co-author Paul M Ridker, MD, MPH, the Eugene Braunwald Professor of Medicine at Harvard Medical school and director of the Center for Cardiovascular disease Prevention at Brigham and Women's Hospital."
"The current work finds that specific genetic signals explain a part of these relationships. We now need to characterize the function of these genetic signals
and therapeutically target individuals at increased risk for developing cardiovascular disease who are also at risk for developing Alzheimer's disease,
Phd, research fellow and radiology resident at the UC San diego School of medicine and the study's first author.
Late-onset AD is the most common form of dementia affecting an estimated 30 million persons worldwide--a number that is expected to quadruple over the next 40 years.
"Currently, there are no disease modifying therapies and much attention has been focused upon prevention and early diagnosis,"said Ole A. Andreassen, MD, Phd,
a senior co-author and professor of biological psychiatry at the University of Oslo in Norway."
"Delaying dementia onset by even just two years could potentially lower the worldwide prevalence of AD by more than 22 million cases over the next four decades,
resulting in significant societal savings
#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,
serendipitously discovered a previously unknown form of human embryonic stem cell. R. Michael Roberts a Curators Professor of Animal Science and a professor of biochemistry,
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."
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.
#Scientists discover protein that boosts immunity to viruses and cancer Scientists have discovered a protein that plays a central role in promoting immunity to viruses
and cancer, opening the door to new therapies. Experiments in mice and human cells have shown that the protein promotes the proliferation of cytotoxic T cells,
which kill cancer cells and cells infected with viruses. The discovery was unexpected because the new protein had known no function
Researchers from Imperial College London who led the study are now developing a gene therapy designed to boost the infection-fighting cells
but when faced with serious infections or advanced cancer, they are often unable to proliferate in large enough quantities to fight the disease.
By screening mice with genetic mutations, the Imperial team discovered a strain of mice that produced 10 times as many cytotoxic T cells
These mice suppressed the infection more effectively and were more resistant to cancer. They also produced more of a second type of T cells,
memory cells, enabling them to recognise infections they have encountered previously and launch a rapid response.
The mice with enhanced immunity produced high levels of a hitherto unknown protein, which the researchers named lymphocyte expansion molecule, or LEM.
They went on to show that LEM modulates the proliferation of human T cells as well as in mice.
The researchers now aim to develop a gene therapy designed to improve immunity by boosting the production of LEM.
Professor Philip Ashton-Rickardt from the Section of Immunobiology in the Department of Medicine at Imperial, who led the study,
Genetically engineering T cells to augment their ability to fight cancer has been a goal for some time and techniques for modifying them already Exist by introducing an active version of the LEM gene into the T cells of cancer patients,
we hope we can provide a robust treatment for patients. ext we will test the therapy in mice,
make sure it is safe and see if it can be combined with other therapies. If all goes well,
we hope to be ready to carry out human trials in about three years. Dr Claudio Mauro
and unlocked an unexpected way of enhancing the ability of our immune system to fight viruses or cancers.
This discovery has immediate consequences for the delivery of innovative therapeutic approaches to cancer. Its ramifications,
however, are far greater as they can help explaining the biological mechanisms of widespread human diseases involving altered immune and inflammatory responses.
Dr Mike Turner, Head of Infection and Immunobiology at The Wellcome Trust, said: he discovery of a protein that could boost the immune response to not only cancer,
but also to viruses, is a fascinating one. Further investigation in animal models is needed before human trials can commence,
odors nor toxic elements that may damage or alter the environment, human health or quality of life are generated,
#Immunotherapy combination promising for untreated patients with advanced melanoma The combination of two immunotherapies for first-line treatment of advanced melanoma induces better responses
Further, the combination was effective in the portion of melanoma patients--the majority--who currently have few effective treatment options. hase 2 clinical trial led by Ludwig Harvard's Stephen Hodi
and Ludwig Memorial Sloan Kettering (MSK)' s Jedd Wolchok has found that the combination of two immunotherapies for first-line treatment of advanced melanoma induces better responses
the combination was effective in the portion of melanoma patients--the majority--who currently have few effective treatment options.
and nivolumab against ipilimumab alone in previously untreated patients, were presented today at the 2015 Annual Meeting of the American Association for Cancer Research
and have been published simultaneously in the New england Journal of Medicine.""Preclinical studies suggested that this combination therapy would have better outcomes than those elicited by their individual
or sequential administration,"said Hodi, who is also director of the Melanoma Center at the Dana-Farber Cancer Institute."
"It's very encouraging to see that pattern reflected in this trial with previously untreated patients."
and is also the Chief of the Melanoma and Immunotherapeutics Service at MSK, found that the same concurrent combination of therapies generated notably positive responses in previously treated patients."
"It was apparent following that trial that the combination should be tested as a first line therapy for metastatic melanoma,
"said Wolchok.""Rationally combined immunotherapies hold great promise for cancer treatment as long as their side effects can be managed."
"Ipilimumab interferes with a process by which the immune system controls the activation of T cells that destroy diseased tissues.
The antibody blocks CTLA-4, a protein switch on the surface of T cells that, when turned on, dampens their activation.
Nivolumab, meanwhile, is an antibody that targets a protein known as PD-1, which is also found on the T cell surface.
PD-1 is engaged often aberrantly by tumor cells themselves to thwart T cell attack. Both drugs have been approved by the US Food and Drug Administration.
The Phase 2, double-blind trial enrolled 142 patients with advanced melanoma who had received not prior therapy.
The tumors of 109 of these patients had the normal form of the gene BRAF
which is mutated frequently in melanoma. This is significant because while melanoma patients with the mutant BRAF gene can be treated with a targeted therapy, the majority
whose tumors encode a normal BRAF have few effective treatment options. In this group of patients, 72 received ipilimumab plus nivolumab, followed by nivolumab alone,
while 37 got ipilimumab plus placebo. Patients whose tumors had a normal BRAF gene showed an overall objective response rate of 61%.
%This included a 22%complete response rate. Those with a normal BRAF who received only ipilimumab had a response rate of 11%,with no complete responses.
Patients with BRAF mutations had similar outcomes for each of the therapies. The combination therapy also induced effects that continued well after the last administration of the therapy.
Of those patients who died, 25 in the combination group (27%)and 17 in the monotherapy group (37%)died from progressive disease.
Notably, three of the deaths in the combination group were determined to have been combined related to the therapy."
"In general, and as might be expected, side effects were more prevalent in patients who received the combination therapy,
"said Hodi.""This is something that will have to be studied further. But we also look forward to following up with the patients who benefitted from the combination therapy to assess the durability of the responses we have observed
#Drugs stimulate body's own stem cells to replace the brain cells lost in multiple sclerosis Led by researchers at Case Western Reserve,
a multi-institutional team used a new discovery approach to identify drugs that could activate mouse
and the other, eczema--were capable of stimulating the regeneration of damaged brain cells and reversing paralysis
when administered systemically to animal models of multiple sclerosis. The results are published online Monday, April 20, in the scientific journal Nature."
"We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis,
but until now, we had no way to direct them to act, "said Paul Tesar, Phd, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics,
and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of medicine."
"Our approach was to find drugs that could catalyze the body's own stem cells to replace the cells lost in multiple sclerosis."
"The findings mark the most promising developments to date in efforts to help the millions of people around the world who suffer from multiple sclerosis.
The disease is the most common chronic neurological disorder among young adults, and results from aberrant immune cells destroying the protective coating, called myelin, around nerve cells in the brain and spinal cord.
Current multiple sclerosis therapies aim to slow further myelin destruction by the immune system, but the Case Western Reserve team used a new approach to create new myelin within the nervous system.
Their work offers great promise of developing therapies that reverse disabilities caused by multiple sclerosis or similar neurological disorders."
"Tesar emphasized that much work remains before multiple sclerosis patients might benefit from the promising approach. Scientists still must find ways to transform the topical medications for internal use
Clobetasol, meanwhile, is typically available by prescription to treat scalp and other skin conditions such as dermatitis.
Neither had been considered previously as a therapeutic for multiple sclerosis, but testing revealed each had an ability to stimulate OPCS to form new myelinating cells.
When administered systemically to lab mice afflicted with a multiple sclerosis-like disease, both drugs prompted native OPCS to regenerate new myelin."
"It was a striking reversal of disease severity in the mice, "said Robert Miller, Phd, a member of the neurosciences faculty at Case Western Reserve who,
This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients."
The team is optimized enthusiastic that versions of these two drugs can be advanced to clinical testing for multiple sclerosis in the future,
"but off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms.
"While multiple sclerosis is the initial focus for translating this research into the clinic, a number of other disorders involve myelin loss
or dysfunction including cerebral palsy, age-related dementia, optic neuritis and schizophrenia. Any drugs developed that enhance myelination in multiple sclerosis also hold promise for benefiting these other disorders."
"The approach from Case Western Reserve University combines cutting-edge stem cell and drug screening technologies to develop new chemical therapeutics for myelin disorders,
"said Christopher Austin, MD, director of the National Center for Advancing Translational Sciences (NCATS) at the National institutes of health (NIH).
include high permeability polymers, nanomagnets for medical diagnostics applications, materials for the 3d printing of metal articles,
#New gene therapy success in a rare disease of the immune system Wiskott-Aldrich syndrome is a rare congenital immune and platelet deficiency
This disease, which primarily affects boys, causes bleeding, severe and recurrent infections, severe eczema and in some patients autoimmune reactions and the development of cancer.
The only treatment available today is bone marrow transplantation, which requires a compatible donor and can itself cause serious complications.
Severe eczema and severe infection disappeared in all cases. Arthritis was eliminated in one patient and another saw major improvement in vasculitis of the lower limbs and was able to return to normal physical activity without a wheelchair.
However, the rate of corrected platelets varies from one patient to another. Fulvio Mavilio, Chief Scientific Officer Genethon:"
"We are all very happy and encouraged by the results of this study. It is the first time that a gene therapy based on genetically modified stem cells is tested in a multicenter, international clinical trial that shows a reproducible and robust therapeutic effect in different centers and different countries.
For very rare diseases such as WAS, multicenter clinical trials are the only effective way of proving the safety
and efficacy of gene therapy and having it rapidly approuved and made available to all patients.
We are following the same approach for other rare and less rare blood diseases.""Frdric Revah, CEO of Genethon, the laboratory of the AFM-Telethon and the trial sponsor, said"These first results of our clinical trial for the treatment of Wiskott Aldrich syndrome are very encouraging.
They illustrate not only the ability of Genethon to carry out the upstream research to develop treatments for these rare and complex diseases,
but also to construct and conduct international clinical trials, to produce these advanced therapy products, to work with international teams and to manage the regulatory aspects of the trials in France and abroad.
These are skills that we implement for other international trials of gene therapy for rare genetic diseases of the immune system
blood, muscle, vision or liver...We will continue the current study with the objective of providing treatment for patients."
"The results obtained in this multicenter clinical trial constitute an important therapeutic advance (overhang) because they concern a complex pathology
which affects almost all of blood cells with dramatic clinical consequences. After transfer of gene, the patients showed a significant clinical improvement due to the reexpression of the protein WASP in the cells of the immune system.
indicates that it is from now on justifiable to hope to treat other complex genetic diseases as those affecting red blood cells."
"This is a very powerful example of how gene therapy can offer highly effective treatment for patients with complex and serious genetic disease.
It also excitingly demonstrates the potential for treatment of a large number of other diseases for
which existing therapies are either unsatisfactory or unavailable
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