#A newly discovered tumor suppressor gene affects melanoma survival Of the hundreds of genes that can be mutated in a single case of melanoma,
only a handful may be true"drivers"of cancer. In research that appeared today in Nature Genetics,
a Weizmann Institute of Science team has revealed now one of the drivers of a particularly deadly subset of melanomas-one that is still seeing a rise in new cases.
This gene is identified a newly member of a group of genes called tumor suppressor genes.
It is mutated in some 5. 4%of melanomas. Furthermore its expression was found to be lost in over 30%of human melanomas;
and this loss, according to the finding, was associated with reduced patient survival. This discovery might open new doors to understanding how this cancer grows and spreads,
and it may lead in the future to new directions in treating this disease. Prof. Yardena Samuels and her team in the Institute's Molecular Cell biology Department were specifically searching for tumor suppressor genes in their database,
which consists of more than 500 melanoma genomes and exomes-protein-building sequences-making it the largest melanoma dataset to date.
As their name suggests, tumor suppressor genes normally inhibit cell growth, including that of cancer cells.
However, when mutated, they act like defective brakes on cellular proliferation. Thus studying these genes is crucial in cancer biology."
"The identification of targetable alterations in melanoma is need an urgent. An in depth understanding of the functional effects of mutations in these genes is the first step toward revealing the underlying mechanism of melanoma growth,
"says Dr. Nouar Qutob, a postdoctoral fellow in Samuels'lab who participated in this research. Indeed, the melanoma genome sequences contained mutations in known tumor suppressor genes,
but there was also a new gene that stood out in the team's search, named RASA2.
The researchers'next step was to conduct a series of functional experiments to understand exactly what this gene does.
They cloned both the normal protein and the most recurrent mutated versions to see their effects on melanoma cells.
They found that RASA2 regulates a key protein in the cell, called RAS. RAS has been identified as a major oncogene that contributes to the unchecked growth of cells.
When they restored the production of the protein in melanoma cells that harbored RASA2 mutations,
these cells stopped growing and eventually died. Patients with dysfunctional RAS pathways tend to have a worse prognosis than those with other types of melanoma,
and, until now, scientists have not managed to create drugs that can target this pathway.""As the RAS pathway is highly dysregulated in cancer,
the discovery of an alternative mechanism for its activation is likely to stimulate an avalanche of further research in this field,
to find out what proteins it communicates with in healthy cells and melanoma, as well as in the cells'response to targeted therapy,
"says Samuels.""Most targeted cancer therapies nowadays work by inhibiting the products of oncogenes that are overactive in melanoma cells.
However, loss or mutations in tumor suppressor genes like RASA2 also contribute to melanoma development;
therefore, discovering and studying RASA2 targets and partners will be our next aim, "says Rand Arafeh,
#DNA in blood can track cancer development and response in real time Scientists have shown for the first time that tumour DNA shed into the bloodstream can be used to track cancers in real time as they evolve
and respond to treatment, according to a new Cancer Research UK study published in the journal Nature Communications today (Wednesday).
Over three years, researchers at the University of Cambridge took surgical tumour samples (biopsies) and blood samples from a patient with breast cancer that had already spread to other parts of her body.
They carefully studied small fragments of DNA from dying tumour cells that are shed into the blood,
comparing them with DNA from the biopsy that was taken at the same point in time. The results show that the DNA in the blood samples matched up with that from the biopsies,
reflecting the same pattern and timing of genetic changes appearing as the cancer developed and responded to treatment.
The results provide the first proof-of-principle that analysing tumour DNA in the blood can accurately monitor cancer within the body.
Study author Professor Carlos Caldas, senior group leader at the Cancer Research UK Cambridge Institute, said:"
"This definitively shows that we can use blood-based DNA tests to track the progress of cancer in real time.
The findings could change the way we monitor patients, and may be especially important for people with cancers that are difficult to reach,
as taking a biopsy can sometimes be quite an invasive procedure.""The patient in the study had had breast cancer that already spread to a number of other organs.
The researchers-part of a collaborative team effort involving the Carlos Caldas and Nitzan Rozenfeld laboratories at the Cancer Research UK Cambridge Institute-were even able to distinguish between the different secondary cancers
and examine how each of the tumours was responding to treatment. Professor Caldas added:""We were able to use the blood tests to map out the disease as it progressed.
We now need to see if this works in more patients and other cancer types,
but this is an exciting first step.""Dr Kat Arney, science information manager at Cancer Research UK, said:"
"Spotting tumour DNA in the bloodstream is a really promising area of research, and has the potential to give doctors valuable clues about a patient's disease without having to take repeated tumour samples."
"For now, surgical biopsies still play an important role in diagnosing and monitoring cancers. But this work gives us a window into the future,
where we'll use less invasive techniques to track the disease in real time
#Scientists paint quantum electronics with beams of light A team of scientists from the University of Chicago
and the Pennsylvania State university have discovered accidentally a new way of using light to draw and erase quantum-mechanical circuits in a unique class of materials called topological insulators.
In contrast to using advanced nanofabrication facilities based on chemical processing of materials, this flexible technique allows for rewritable'optical fabrication'of devices.
Thompson was referred to the University of Michigan's C. S. Mott Children's Hospital where doctors had to decide
doctors were able to use a 3-D printer to print models of the fetus face,
The case is outlined in the November issue of Pediatrics.""Based on the images we had, it was unclear
"says senior author Glenn Green, M d.,associate professor of pediatric otolaryngology at U-M's C. S. Mott Children's Hospital."
in order to make clinical decisions. 3-D printing may be an incredibly valuable tool to help doctors prepare for complex cases ahead of birth."
"The extra information gained from the 3-D printed models helped doctors determine that Conan would not need what's called an Ex Utero Intrapartum Treatment Procedure (EXIT.
so that a surgeon can establish an airway to allow the baby to breathe. Instead, Conan was born via a scheduled C-section."
I didn't need the more complicated and risky surgery and could be awake for the birth of my first baby.
"All procedures were done at U-M's C. S. Mott Children's Hospital. The computer designs for the models were created in the lab of Scott Hollister, Ph d,
. professor of biomedical engineering and mechanical engineering and associate professor of surgery at U-M. The models were printed by Ann arbor-based Thingsmiths.
of the U-M division of Otolaryngology-Head and Neck Surgery. 3-D printing has had many medical applications.
Green and Hollister are leading efforts to design customized medical implants for those and other patients s
#New field of application for versatile helper In Alzheimer's disease proteins clump together to long fibrils causing the death of nerve cells.
Scientists, therefore, hope to deploy them as agents in the treatment of neurodegenerative diseases. Using the example of a small heat shock protein,
Promising candidate for new forms of therapy The helper proteins are true multi-talents. They can bind large numbers of badly folded proteins
This also includes the potentially disease-causing proteins that collect in the cells of patients with neurodegenerative disorders--for example
Heat shock proteins are associated also with other nervous system disorders like Parkinson's disease and multiple sclerosis. Although it is still unclear what role these catastrophe aid workers play in the various ailments,
If the precise mechanisms by which these heat shock proteins hook up to their disease-causing counterparts were known,
scientists could deploy this knowledge to develop agents utilizing these mechanisms to fight disease. Two ways out of the chaos A group of researchers led by Bernd Reif
it would improve their ability to attach to the disease-causing fibrils--a first step in the development of new agents against Alzheimer's and other neurodegenerative diseases.
#CWRU researcher lands grant to build stealthy brain tumor treatment A Case Western Reserve University researcher has received a 5-year,
stealth bombs that slip past the brain's defenses to attack an incurable form of cancer.
Efstathios Karathanasis, a biomedical engineer at Case School of engineering, has developed chainlike nanoparticles that can carry drugs across the blood-brain barrier that keeps standard medicines from reaching their target--a highly aggressive brain cancer called
The nanochains will tote bombs of chemotherapy medicine and glioblastoma stem cell inhibitors identified by Jeremy Rich,
MD, chairman of the Department of Stem Cell biology and Regenerative medicine at Cleveland Clinic Lerner Research Institute.
The researchers expect the chemotherapy will destroy the majority of tumor cells and the inhibitor will eliminate cancer cells that are resistant
and can cause brain tumors to reoccur. Their goal is to develop a treatment that eradicates the cancer with one safe dose."
"The grant enables our labs to integrate our technologies, "Karathanasis said.""We need integration to solve this problem."
"Glioblastoma multiforme is the most common and most malignant tumors of glial cells, which provide structure to the brain.
The median survival rate among adults is just under 15 months, according to the American Brain Cancer Association.
when tumors are present, preventing drugs from crossing from the blood stream into the diseased tissue.
And"surgeons can't go in and cut liberally,"Karathanasis said.""Brain tumor cells are often invasive and spread throughout the normal brain,
and drugs--if they get in--do nothing because of resistance that develops.""To reach inside tumors, Karathanasis'lab developed a short chain of magnetic nanoparticles made of iron oxide
and modified the surfaces so one links to the next, much like Lego building blocks. They link three
and attach to the tumors'vascular walls. When nanochains congregate inside a tumor, the researchers place a wire coil,
called a solenoid, outside near the tumor. Electricity passed through the solenoid creates a weak radiofrequency field.
The field causes the magnetic tails of the chain to vibrate bursting the liposome spheres,
releasing their drug cargo into the brain tumors. In testing with mouse models of aggressive brain tumors, the technology took out far more cancer cells, inhibited tumor growth better and extended life longer than traditional chemotherapy delivery.
The targeted delivery system also used far less drug than used in traditional chemotherapy, saving healthy tissue from toxic exposure.
To treat glioblastoma multiforme, which typically produces cells resistant to chemotherapy, the team will add inhibitors to traditional chemotherapy drugs.
and to form tumors. Normal neural cells do not. In testing with mouse models of the cancer, models injected with an inducible nitric acid synthase inhibitor had fewer and smaller tumors compared to control models.
In addition to the grant money, the researchers will have access to the National Cancer Institute's Alliance for Nanotechnology in Cancer,
and will exchange ideas and resources, Karathanasis said. The Karathanasis and Rich labs will work with Mark Griswold, professor of radiology at Case Western Reserve School of medicine,
who will build radiofrequency systems. Ketan Ghaghada, assistant professor of radiology at Baylor College of Medicine, will guide
and oversee the steps taken to translate the research toward clinical trials. Over the next five years
or writing information on a memory chip is done within a single memory cell, without bleeding over into neighboring cells.
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
flow cytometry and fluorescent tagging, the high cost and infrastructure requirements of these techniques largely limit them to laboratory settings--something point-of-care diagnostics aims to fix.
Her research today involves translating molecular imaging research to point-of-care diagnostics--describes the fluorescence microscope system this week in a paper published in Biomedical Optics Express, from The Optical Society.
Biomedical scientists at UC Santa barbara and the Sanford-Burnham-Prebys (SBP) Medical Discovery Institute have discovered now a mechanism by
and disease, appear today in the Proceedings of the National Academy of Sciences.""This is a fundamental advance that is broadly applicable
and thereby maintain health as well as contribute to various diseases.""This newly discovered mechanism encompasses multiple factors,
blood coagulation and immunity. Honing in on individual examples, the researchers were able to track each of them through time
which we increasingly note is occurring at the interface of health and disease, "Marth explained."
"In retrospect from published literature and from studies in progress, we can now see how sepsis,
diabetes and inflammatory bowel disorders can arise by the targeted acceleration or deceleration of secreted protein aging and turnover."
"The discovery of this mechanism provides a unique window into disease origins and progression,"Marth added."
"It has been known that circulating glycosidase enzyme levels are altered in diseases such as sepsis, diabetes, cancer and various inflammatory conditions.
We are beginning to see previously unknown molecular pathways and connections in the onset and progression of disease
#Gene on-off switch works like backpack strap A research team based in Houston's Texas Medical center has found that the proteins that turn genes on by forming loops in human chromosomes work like the sliding plastic adjusters on a grade-schooler
This discovery could provide new clues about genetic diseases and allow researchers to reprogram cells by directly modifying the loops in genomes.
The multi-institutional group includes researchers from Baylor College of Medicine Rice university, Stanford university and the Broad Institute.
Rao likened the result to a new form of genome surgery: a procedure that can modify how a genome is folded by design and with extraordinary precision."
or biological implant, engineers strive to make the material strong and defect-free. However, methods conventionally used to control the amount of defects in a material,
or mechanical stress, can also have undesirable consequences in terms of the material's strength, structure and performance.
#From good to bad with a copper switch At the molecular level, the difference between Doctor Jekyll and Mr Hyde lies in a metal, copper.
and animals (it is responsible for neurodegenerative diseases such as spongiform encephalopathies). According to a new SISSA study, the mechanism underlying this change is a metal, copper,
"nor do we know any treatments to cure prion diseases. Our research has uncovered finally a critical cofactor,
"On that occasion, we hypothesized that the pathological genetic mutations present in the prion protein could affect copper coordination".
(or"bad")form capable of causing degeneration of nervous tissue and diseases, some of which very severe.
Among the diseases are Creutzfeld Jakob disease in humans and"mad cow disease in cattle. Unique in nature
steel braces straighten crooked teeth, steel scalpels remove tumors. Most of the goods we consume are delivered by ships
Steel surgical tools can still carry microorganisms that cause deadly infections. Now researchers at the Harvard John A. Paulson School of engineering and Applied sciences (SEAS) have demonstrated a way to make steel stronger, safer and more durable.
and avenues for commercialization, including non-fouling medical tools and devices, such as implants and scalpels, nozzles for 3d printing and, potentially, larger-scale applications for buildings and marine vessels.
Medical steel devices are one of the material's most promising applications, said Philseok Kim,
and cofounder and vice president of technology AT SEAS spin-off SLIPS Technologies Inc."Because we show that this material successfully repels bacteria and blood, small medical implants,
and skin cancers Scientists from the University of Granada (UGR) have patented an effective drug for treating cancer stem cells (CSCS) in breast, colon, and skin cancers.
The researchers have proved the anti-tumor effects of the drug on immunodeficient mice. The new compound and its derivatives enabled the researchers to reduce tumor activity by 50 percent after 41 days of treatment with the drug,
administered twice a week, to mice with induced tumors. They have managed also to successfully describe the mechanisms by which the drug acts on the cancer stem cells (CSCS.
This crucial scientific breakthrough has been made by the UGR research groups"Research and development of Pharmaceutical Drugs, "directed by Professor Joaquín Campos Rosa, and"Advanced Therapies:
Differentiation, Regeneration and Cancer",directedby Professor Juan Antonio Marchal Corrales. The Córdoba-based company Canvax Biotech has participated also in the development of the patent.
A nontoxic drug One of the major advantages of the drug is that it is nontoxic.
Despite being administered to the mice in high concentrations (150 milligrams per kilo), no adverse effects were observed in the healthy cells.
Moreover, from a pharmaceutical perspective this anti-tumor drug can be produced successfully in large quantities. The researchers were able to obtain the required amount of the synthesis in just five days.
the scientists had managed already to create an effective drug (called Bozepinib) for treating cancer stem cells,
which maintains the biological activity of its predecessor as an effective anti-tumor drug, but which can also be synthesized
In order to be able to test the new drug on mice and gauge its effectiveness on human tumors,
first of all they had to inject human tumor cells into immunodeficient mice (to ensure they did not reject these cancerous cells).
they discovered that some of the compounds effectively inhibited the growth of the tumor cells and the migration ability of these cells to other healthy tissues,
a huge advantagewhen compared to other cancer treatments such as chemotherapy. Althoughcscs are only found in small quantities in tumors,
from a clinical perspective the ability to target them directly is of fundamental importance, given that they are responsible for originally causing the tumor, relapses and resistance to anticancer treatments.
The next step: Lungs and pancreas Having proved the preclinical effectiveness of the new drug in treating cancer stem cells in breast, colon,
and skin cancers, the scientists will proceed now to study the drug's effect on lung and pancreas cancers, two of the most aggressive types.
They must also complete further ADME-Tox("absorption, distribution, metabolism, excretion and toxicity")studies of the compound's behavior within the organism, a necessary step before carrying out clinical trials.
In the last two months, the research project has received funding of over#124,930 from the public sector from the Ministry of Economy and Finance and the firm Canvax Biotech SL and#20
3-D cell growth opens new pathway for spinal cord repair Griffith University researchers have opened a new avenue to advance a therapy to repair the paralysed spinal cord.
which cells are transplanted into the injury site, "says research supervisor Dr James St john, from Griffith's Eskitis Institute for Drug Discovery.
"In Australia, more than 12,000 people live with spinal cord paralysis and there is at least one new occurrence every day,
."Although rehabilitation medicine has resulted in reductions in mortality, the current outcome for patients is permanent paralysis, with an overall cost to the community of $2 billion a year."
"In light of the overwhelming impact of spinal cord injury, new therapeutic interventions for drug discovery and cell therapy are needed urgently."
"The transplantation of the specialised cell type from the olfactory (sense of smell) system is a promising approach to spinal cord repair."
thus demonstrating this therapy can work, "says Mr Vadivelu.""What is needed now is to make the transplantation therapy more effective and suitable for patients with a range of different spinal cord injuries."
"The new method enables transplanted cells to survive and better integrate into the injury site.
In turn, this will help the spinal cord to regenerate more effectively.""Liquid marbles are a remarkably simply way to culture cells in 3d,
"Burnes probably didn't think they could be used to help develop a therapy for spinal cord repair,
highly sensitive magnetometers intended for life science and medical applications
#Scientists gain insight into origin of tungsten-ditelluride's magnetoresistance Scientists recently discovered that tungsten ditelluride (WTE2) is electronically three-dimensional with a low anisotropy.
or high risk atherosclerotic plaques--inflamed fatty deposits in the artery wall and a main contributor to cardiovascular disease (CVD).
and causing a heart attack or stroke. CVD remains the leading cause of morbidity and mortality in developed nations,
despite advances in diagnosis and treatment. Atherosclerosis is an important contributor to CVD and varies in severity depending on multiple features that contribute to plaque progression and"stability."
Atherosclerosis is a complex disease with many stages, ranging from plaques that can remain clinically silent for decades("stable")to dangerous("vulnerable")plaques.
although few focus on the important clinical endpoint of thrombosis.""Our results showed that the fluorescence ACPP probes were able to distinguish high risk plaques with high sensitivity
"explained corresponding author James Hamilton, Phd, professor of physiology and biophysics and research professor of medicine at BUSM."
#New drug candidate is promising therapeutic option for angiogenic retinal diseases A research team led by scientists at Beth Israel Deaconess Medical center (BIDMC)
and retinopathy of prematurity (ROP) by preventing the overgrowth of blood vessels that are characteristic of these two retinal diseases.
The new findings, described in today's issue of the journal Science Translational Medicine, show that this molecule,
a discovery that offers a promising alternative to current therapies for these retinal diseases, which require monthly injections of large molecules directly into the eyeball."
"Angiogenesis, the abnormal overgrowth of blood vessels, underlies many severe diseases, and when angiogenesis develops in the eye's retina it causes decreased vision
and can even lead to blindness, "said the study's corresponding author Richard L. Sidman, MD, an investigator in the Department of Neurology at BIDMC and Bullard Professor of Neuropathology (Neuroscience), Emeritus, at Harvard Medical school.
Sidman is a leader in the field of mammalian brain development whose studies have focused on disease mechanisms in mouse neuro-genetic disorders,
including disorders of the retina, the light-sensitive layer of brain tissue at the inner surface of the back of the eye that transmits image information to other parts of the brain via the optic nerve.
AMD develops in approximately 14 million older individuals throughout the U s. This overgrowth of blood vessels damages the photoreceptor cells near the center of the eye's retina,
who develop a similar retinal disease as a side effect of high-level oxygen treatments used until their lungs develop sufficiently to handle the much lower oxygen levels in room air.
when the agent was administered by either systemic injection, or through eye drops.""Under normal circumstances, a protein called vascular endothelial growth factor VEGF binds to pertinent endothelial cell receptors lining the blood vessels,
"Although a few other anti-VEGF drugs have been approved for therapy of AMD, they must be delivered directly into the eye through monthly intravitreal injections."
"These treatments are costly, require highly skilled professional execution, and, in rare cases, can cause bleeding
or infection in the eye,"said Sidman. Furthermore, he added, not all patients respond to these agents and, for many patients,
responsiveness decreases after about six months.""In addition to future clinical trials on AMD and ROP, we think that diabetic retinopathy
and certain forms of cancer may also prove to be responsive to Vasotide, "said Sidman."
"This is a very exciting development in that it has the potential to allow the self-administration of a sight-saving drug to patients with AMD,
"said Harold F. Dvorak, MD, Mallinckrodt Distinguished Professor of Pathology at HMS and BIDMC, whose laboratory first identified the VEGF signaling protein nearly 30 years ago o
safe for treatment-resistant autoimmune blood conditions The immunosuppressant sirolimus is an effective and safe steroid-sparing therapy for children and young adults with highly treatment-resistant autoimmune blood conditions,
according to a study published online today in Blood, the Journal of the American Society of Hematology (ASH).
This treatment is particularly effective in children with autoimmune lymphoproliferative syndrome (ALPS), a chronic genetic disorder characterized by the buildup of white blood cells in the organs.
Patients with ALPS and other autoimmune disorders often have immune systems that destroy their body's own healthy blood cells.
The resulting decrease in blood cells causes symptoms such as anemia, uncontrolled bleeding, and infection. Few effective and well-tolerated therapies exist to manage these chronic autoimmune issues.
While standard immunosuppressive therapy with corticosteroids may help some patients, others are resistant, intolerant, or cannot successfully maintain healthy blood cell counts
when they discontinue medication. Recently investigators reported that sirolimus successfully resolved these autoimmune conditions in a small group of children with ALPS without causing adverse side effects."
or white blood cells,"said senior study author David Teachey, MD, of the Children's Hospital of Philadelphia."
as they are associated often with long-term health effects, such as osteoporosis and higher risk of infection."
"To improve disease management for patients with ALPS and similar autoimmune disorders, a research team led by Teachey and his colleague Karen Bride, MD,
After six months, those who benefited from the drug were allowed to continue treatment with continued follow-up appointments to monitor toxicities.
Based on these findings, the authors propose use of sirolimus as early therapy for patients with these chronic treatment-resistant autoimmune blood conditions
sirolimus should be considered an early therapy option for patients with autoimmune blood disorders requiring ongoing therapy
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