#Personalized cellular therapy achieves complete remission in 90 percent of acute lymphoblastic leukemia patients studied Ninety percent of children
or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy CTL019 developed at the Perelman School of medicine at the University of Pennsylvania.
The results are published this week in The New england Journal of Medicine. The new data which builds on preliminary findings presented at the American Society of Hematology's annual meeting in December 2013 include results from the first 25 children and young adults (ages 5 to 22
) treated at the Children's Hospital of Philadelphia and first five adults (ages 26 to 60 treated at the Hospital of the University of Pennsylvania.
Twenty-seven of the 30 patients in the studies achieved a complete remission after receiving an infusion of these engineered hunter cells
whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left said the study's senior author Stephan Grupp MD Phd a professor of Pediatrics in Penn's Perelman School of medicine and director of Translational Research in the Center
for Childhood Cancer Research at the Children's Hospital of Philadelphia. The durable responses we have observed with CTL019 therapy are unprecedented.
Shannon Maude MD Phd an assistant professor of Pediatrics and a pediatric oncologist at CHOP and Noelle Frey MD MSCE an assistant professor of Medicine and an oncologist at Penn's Abramson's Cancer Center
are co-first authors of the new study. The research team is led by Carl June MD the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center
along with David Porter MD the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center.
CTL019 manufacturing begins with a patient's own T cells which are collected via an apheresis process similar to blood donation then reprogrammed in Penn's Clinical Cell
and Vaccine Production Facility with a gene transfer technique that teaches the T cells to target
and kill tumor cells. The engineered cells contain an antibody-like protein known as a chimeric antigen receptor (CAR)
which is designed to bind to a protein called CD19 found on the surface of B cells including the cancerous B cells that characterize several types of leukemia.
The modified hunter cells are infused then back into the patient's body where they both multiply
and attack the cancer cells. A signaling domain built into the CAR promotes rapid multiplication of the hunter cells building an army of tumor-killing cells that tests reveal can grow to more than 10000 new cells for each single engineered cell patients receive.
Nineteen patients in the study remain in remission 15 with this therapy alone including a 9 year old who was the first ALL patient to receive the therapy more than two years ago.
The follow-up periods reported in the study are more than six months for most patients with a range from 1. 4 to 24 months.
Five patients went off-study for alternate therapy three of whom proceeded to allogeneic stem cell transplants while in remission.
Seven patients relapsed between 6 weeks and 8. 5 months after their infusions including three
whose cancers returned as CD19-negative leukemia that would not have been targeted by the modified cells.
All patients who received the CTL019 hunter cells experienced a cytokine release syndrome (CRS) within a few days after receiving their infusions--a key indicator that the engineered cells have begun proliferating and killing tumor cells in the body.
which included varying degrees of flu-like symptoms with high fevers nausea and muscle pain.
which also express the CD19 protein had been eliminated along with their tumors. The researchers note that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the gene-modified T cells
which are thought to provide long-term vaccine-like activity preventing tumor recurrence. Since B cells play a role in helping fight infection patients typically receive immunoglobulin replacement to maintain healthy immune function.
Our results support that CTL019 can produce long-lasting remissions for certain heavily pre-treated ALL patients without further therapy Frey said.
For our patients who have relapsed already after stem cell transplants or don't have any options for donors this option has provided new hope.
In July 2014 the U s. Food and Drug Administration granted CTL019 its Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric ALL a step
which is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions if a therapy has demonstrated substantial advantages over available treatments.
CTL019 is personalized the first cellular therapy to receive the designation. The first multicenter CTL019 trial has opened recently in the U s
. and additional multisite trials are expected to initiate by the end of the year. Story Source:
and cells offer new solutions for cancer diagnosis and therapy. Understanding the interdependency of physiochemical properties of nanomedicines in correlation to their biological responses
and functions is crucial for their further development of as cancer-fighters. To develop next generation nanomedicines with superior anticancer attributes we must understand the correlation between their physicochemical properties--specifically particle size
or smaller--exhibited enhanced performance in vivo such as greater tissue penetration and enhanced tumor inhibition. Over the last 2-3 decades consensus has been reached that particle size plays a pivotal role in determining their biodistribution tumor penetration cellular internalization clearance from blood plasma and tissues as well as excretion from the body--all of
which impact the overall therapeutic efficacy against cancers stated Li Tang first author of this PNAS article.
Our studies show clear evidence that there is an optimal particle size for anticancer nanomedicines resulting in the highest tumor retention.
Among the three nanoconjugates investigated the 50 nm particle size provided the optimal combination of deep tumor tissue penetration efficient cancer cell internalization as well as slow tumor clearance exhibits the highest efficacy against both
primary and metastatic tumors in vivo. To further develop insight into the size dependency of nanomedicines in tumor accumulation
and retention the researchers developed a mathematical model of the spatiotemporal distribution of nanoparticles within a spherically symmetric tumor.
The results are extremely important to guide the future research in designing new nanomedicines for cancer treatment Cheng noted
In addition a new nanomedicine developed by the Illinois researchers--with precisely engineered size at the optimal size range--effectively inhibited a human breast cancer
and prevented metastasis in animals showing promise for the treatment of a variety of cancers in humans.
Seitz Materials Research Laboratory and University of Illinois Cancer Center. Tang who obtained his Phd degree from the University of Illinois with Jianjun Cheng is currently a CRI Irvington postdoctoral fellow at the Massachusetts institute of technology.
Collaborators and co-corresponding authors of the paper at Illinois include Timothy Fan associate professor veterinary clinical medicine;
#New mechanism that can lead to blindness discovered An important scientific breakthrough by a team of IRCM researchers led by Michel Cayouette Phd is being published by The Journal of Neuroscience.
These findings could have a significant impact on our understanding of retinal degenerative diseases that cause blindness.
This is important because the death of photoreceptor cells is known to cause retinal degenerative diseases in humans that lead to blindness.
We believe our results could eventually have a substantial impact on the development of treatments for retinal degenerative diseases like retinitis pigmentosa
and Leber's congenital amaurosis by providing novel drug targets to prevent photoreceptor degeneration concludes Dr. Cayouette.
According to the Foundation Fighting Blindness Canada millions of people in North america live with varying degrees of irreversible vision loss
and power wearable sensors or medical devices or perhaps supply enough energy to charge your cell phone in your pocket says James Hone professor of mechanical engineering at Columbia and co-leader of the research.
The odorless tasteless element can cause skin discoloration stomach pain partial paralysis and a range of other serious health problems.
and can be collected easily in places where public smoking is allowed it could be part of a low-cost solution for a serious public health issue they say.
#Researchers look to exploit females natural resistance to infection Researchers have linked increased resistance to bacterial pneumonia in female mice to an enzyme activated by the female sex hormone estrogen.
Females are naturally more resistant to respiratory infections than males. Now an international team of scientists has shown that increased resistance to bacterial pneumonia in female mice is linked to the enzyme nitric oxide synthase 3 (NOS3.
They also show that this enzyme is activated ultimately by the release of the female sex hormone estrogen.
The team lead by Professor Lester Kobzik at the Harvard university School of Public health introduced Streptococcus pneumoniae into the lungs of mice to mimic the inhalation of bacteria that occurs naturally as we breathe.
They found that deleting this gene meant that the female mice were no longer more resistant to infection.
The team hope that in the future this knowledge could be used to enhance resistance to common and serious lung infections.
Ultimately this work could be especially useful in reducing risk of secondary bacterial pneumonias during seasonal
or pandemic influenza said Professor Lester Kobzik the senior author. We were pleased quite that the work led us to NOS3-targeting drugs that are already available
and that can indeed improve resistance to pneumonia in our mouse model l
#Researchers turn to 3-D technology to examine the formation of cliffband landscapes A blend of photos
Mapping that dense molecular machinery is one of the most promising and challenging frontiers in medicine and biology.
Errors in copying DNA are found in certain cancers and this work could one day help develop new treatment methods that stall
The structural knowledge may help others engineer small molecules that inhibit DNA replication at specific moments leading to new disease prevention
#Tool enhances social inclusion for people with autism The University of Alicante has developed together with centres in the UK Spain
and Bulgaria a tool designed to assist people with autism spectrum disorders by adapting written documents into a format that is easier for them to read
and social inclusion of the users as they gain better access to education employment health care and social activities she adds.
Although in principle the tool has been designed for people with autism spectrum disorders who generally have difficulties in areas such as communication social interaction
#Prostate cancers penchant for copper may be a fatal flaw Like discriminating thieves prostate cancer tumors scavenge
Researchers at Duke Medicine have found a way to kill prostate cancer cells by delivering a trove of copper
The combination approach which uses two drugs already commercially available for other uses could soon be tested in clinical trials among patients with late-stage disease.
This proclivity for copper uptake is something we have known could be an Achilles'heel in prostate cancer tumors as well as other cancers said Donald Mcdonnell Ph d. chairman of the Duke Department of Pharmacology and Cancer Biology and senior author
of a study published Oct 15 2014 in Cancer Research a journal of the American Association of Cancer Research.
Our first efforts were to starve the tumors of copper but that was unsuccessful. We couldn't deplete copper enough to be said effective Mcdonnell.
and then use a drug that requires copper to be effective to attack the tumors.
Mcdonnell and colleagues searched libraries of thousands of approved therapies to identify those that rely on copper to achieve their results.
Disulfiram had at one time been a candidate for treating prostate cancer--it homes in on the additional copper in prostate cancer tumors
--but it showed disappointing results in clinical trials among patients with advanced disease. The Duke team found that the amount of copper cancer cells naturally hoard is not enough to make the cells sensitive to the drug.
along with the disulfiram the combination resulted in dramatic reductions in prostate tumor growth among animal models with advanced disease.
Androgens the male hormones that fuel prostate cancer increase the copper accumulation in the cancer cells.
or similar compounds and copper especially beneficial for men who have been on hormone therapies that have failed to slow tumor growth.
Unfortunately hormone therapies do not cure prostate cancer and most patients experience relapse of their disease to a hormone-refractory
or castration-resistant state Mcdonnell said. Although tremendous progress has been made in treating prostate cancer there is clearly a need for different approaches
and our findings provide an exciting new avenue to explore. Mcdonnell said clinical trials of the combination therapy are planned in upcoming months.
Andrew Armstrong M d. associate professor of medicine was involved with a recent study at Duke testing disulfiram in men with advanced prostate cancer.
While we did not observe significant clinical activity with disulfiram in men with recurrent prostate cancer in our recent clinical trial this new data suggests a potential way forward
and a reason why this trial did not have more positive results Armstrong said. Further clinical studies are warranted now to understand the optimal setting for combining copper with disulfiram
or similar compounds in men with progressive prostate cancer particularly in settings where the androgen receptor is active.
The above story is provided based on materials by Duke Medicine e
#Earths magnetic field could flip within a human lifetime Imagine the world waking up one morning to discover that all compasses pointed south instead of north.
Flip could affect electrical grid cancer ratesthe discovery comes as new evidence indicates that the intensity of Earth's magnetic field is decreasing 10 times faster than normal leading some geophysicists to predict a reversal within a few
or temporary loss of the field before a permanent reversal could increase cancer rates. The danger to life would be even greater
#Immune cells in liver drive fatty liver disease, liver cancer Fatty liver disease--alongside fatty liver due to massive alcohol consumption--is caused mainly by excessive consumption of fat
This is referred to as nonalcoholic fatty liver disease (NAFLD. If NAFLD becomes chronic--e g. through the constant uptake of high lipids
This can lead to nonalcoholic steatohepatitis (NASH)--a liver disease with clear detectable pathologic alteratons of the tissue.
These liver diseases (NAFLD and NASH) along with chronic viral infections are the most common causes of liver cancer or hepatocellular carcinoma (HCC.
In the United states HCC is the fastest-growing form of cancer at the moment. No efficient causal therapy exists for HCC patients of which approximately 800000 die every year.
T cells involved in the development of fatty liver disease NASH and HCC The mechanisms that cause diseases such as fatty liver disease steatohepatitis and HCC are still not widely understood.
However immune cells particularly CD8+T cells and NK T cells seem to play an important role.
This finding was made by a team of scientists led by Prof. Mathias Heikenwälder Prof. Matthias Tschöp Dr. Kerstin Stemmer Dr. Kristian Unger Prof.
Achim Weber from Zurich University Hospital and Dr. Monika Wolf Institute of Surgical Pathology University Hospital Zurich.
The animal model which was used to examine the long-term effects of metabolic syndrome*enabled the scientists to elucidate new mechanisms that cause fatty liver disease
and also show how it can develop into liver cancer. Inflammatory events offer starting point for prevention
The inflammation which is triggered by specific immune cells encourages the progression of fatty liver pathology
Our results provide completely new insights into the development of these serious liver diseases. Building on this knowledge we now want to develop new preventive
and therapeutic strategies to combat these diseases. The initial studies are already under way in the preclinical model.*
*Metabolic syndrome: a combination of obesity/abdominal adiposity insulin resistance raise levels of lipids in the blood and raised blood pressure.
Story Source: The above story is provided based on materials by Helmholtz Zentrum München-German Research center for Environmental Health.
At least if they live in central neighbourhoods with good access to medical services and public transit infrastructure they will not suffer so much from the loss of automobility.
#Defective gene renders diarrhea vaccine ineffective Acute diarrheal illnesses cause nearly one-fifth of all child deaths in developing countries.
Improved sanitation and hygiene have had limited a effect on the spread of the illness. Today vaccination is considered the most important method for reducing mortality.
Unfortunately several studies have shown that the two available living vaccines Rotarix and Rotateq which are recommended by bodies including the World health organization are not sufficiently effective in developing countries.
In many African countries protection has been as low as 20-50%.%The current study to be published in the Journal of Clinical Infectious diseases by Johan Nordgren from Professor Lennart Svensson's research group shows that up to four of ten children in Burkina faso are genetically resistant to the virus strains found in the vaccines.
The researchers found that children who can not express a particular sugar molecule in the small intestine called the Lewis molecule do not become infected by the rotavirus types found in existing vaccines.
This Lewis molecule is needed probably as a receptor for the rotavirus to be able to enter
This means that these children do not get the desired immunological protection from the vaccine.
and can greatly impact the evaluation of the rotavirus vaccines now being introduced in several developing countries.
The results could lead to a review of the vaccine composition and the development of vaccines better suited to the populations most affected by rotavirus.
Story Source: The above story is provided based on materials by Linköping University. Note: Materials may be edited for content and length.
#Discovery of cellular snooze button advances cancer, biofuel research The discovery of a cellular snooze button has allowed a team of Michigan State university scientists to potentially improve biofuel production and offer insight on the early stages
of cancer. The discovery that the protein CHT7 is a likely repressor of cellular quiescence
and oil production also wields control of cellular growth--and tumor growth--in humans. Christoph Benning MSU professor of biochemistry and molecular biology and his colleagues unearthed the protein's potential
Its application in cancer research however was a surprise finding that is leading Benning's lab in a new direction.
and study algae which have the genomic repertoire that make them relevant in their capacity to drive advances in human medicine.
when it's under stress said Chia-Hong Tsai doctoral candidate with MSU's Department of energy Plant Research Laboratory
In terms of human medicine this discovery gives scientists a promising new model to study tumor suppression and growth.
For cancer research it's a new paradigm Benning said. The switch that tells an organism to grow
That is the first step of tumor growth. Story Source The above story is provided based on materials by Michigan State university.
and health services. In addition the market is strong for nearly all types of new degree-holders.
Biomedical applications include microfluidic devices that can handle and process very small volumes of liquid such as samples of saliva or blood for diagnostics.
#Research leads to brain cancer clinical trial Researchers at the University of Calgary's Hotchkiss Brain Institute (HBI)
and Southern Alberta Cancer Research Institute (SACRI) have made a discovery that could prolong the life of people living with glioblastoma--the most aggressive type of brain cancer.
Samuel Weiss Phd Professor and Director of the HBI and Research Assistant professor Artee Luchman Phd and colleagues published their work today in Clinical Cancer Research
Researchers used tumour cells derived from 100 different glioblastoma patients to test drugs that could target the disease.
Researchers used the new therapy to inhibit a pathway in the cancer cells known as mtor signaling--putting the brakes on this pathway combined with the current standard therapy caused more of the cancer cells to die.
and therapies that can be tested in the clinic provides the greatest hope for brain cancer patients
and their families says Weiss leader of the university's Brain and Mental health strategic research priority.
Glioblastoma is the most common and deadly form of brain cancer among adults. The progression and complexity of the tumours are often difficult to treat.
and Dr. Greg Cairncross--director of SACRI and leader of the Terry Fox Research Institute (TFRI'Therapeutic Targeting of Glioblastoma research program at the university--are now working with cancer researchers Dr. Warren Mason (Princess
Margaret Cancer Centre in Toronto) and Dr. Lesley Seymour (Director of the NCIC Clinical Trials Group's Investigational New Drug Program) and drug manufacturer Astrazeneca to plan a clinical trial testing a similar but newer drug
This is an important initiative--to test new drugs being developed for other types of cancers in the laboratory to identify which are most promising for testing in patients with glioblastoma.
which will be funded by a grant from the TFRI as well as grants from Canadian Cancer Society Research Institute to NCIC CTG says Seymour r
Fast accurate and affordable DNA sequencing is the first step toward personalized medicine. Threading a DNA molecule through a tiny hole called a nanopore in a sheet of graphene allows researchers to read the DNA sequence;
Olfactory loss is often an early symptom in a variety of neurological disorders including Alzheimer's and Parkinson's diseases.
and given its connection to other brain regions it could lend insight into the relationship between olfactory loss and many brain disorders.
#Timing is key for traumatic brain injury treatment Researchers at the University of Adelaide have discovered two potential treatments for traumatic brain injury that are most effective
when given at different stages after the injury has occurred. Laboratory studies conducted in the University's School of Medical sciences have confirmed that changes in brain water channels over time play a critical role in traumatic brain injury.
For his Phd at the University researcher Dr Joshua Burton tested two compounds that alter the natural flow of water activity in and out of the brain.
He found that recovery from brain injury can be assisted greatly when these compounds are given at the right times.
Dr Burton's work could point to the potential development of new drugs as well as new approaches to preventing brain damage and death.
One of the serious consequences of traumatic brain injury is an increase in brain moisture content and associated brain swelling which significantly impacts patients'neurological outcomes.
This swelling can occur for days after the initial injury and is frequently life-threatening Dr Burton says.
but in the case of traumatic injury or stroke they become a pathway of vulnerability that allows swelling.
A second drug used later in the progression of the injury acts to enhance the water channel activity letting superfluous moisture out when needed.
By using both of these compounds--a blocker at the early stage of injury and an activator at the later stage--we're able to complement the brain's natural healing processes
because it clarifies the roles of aquaporins in the brain during the short and long-term responses to traumatic head injury.
Most current therapeutic approaches are limited in their ability to reduce injury-induced brain swelling and no treatments are available to resolve excess fluid at a later stage.
New approaches that can improve the outlook for patients especially in the later stages of injury development would be of great benefit she says.
Insects use proteins that bind to the surface of pathogens to detect infections in their body.
For example when a mosquito transmits a pathogen like malaria the parasite that causes the disease spends part of its life in the mosquito's blood Kanost said.
This process is important in fully understanding how insects transmit diseases and how their immune system interacts with the pathogens they are transmitting
so that we can disrupt it. Researchers studied a protein called beta-13-glucan recognition protein or GRP from the blood of a caterpillar.
This protein complex on the surface of the pathogen may form a platform for attracting
and activating other proteins from the blood triggering immune responses that help kill pathogens in an insect's blood The findings may lead to new ways to control disease transmission from insects to humans and animals as well as new methods for biocontrol
which one molecule activates another molecule leading to production of chemicals that kill pathogens. Researchers used a variety of biochemical and biophysical experiments to understand how the protein molecules assemble on the surface of the pathogen.
They found that clusters of five GRP protein molecules bind to a polysaccharide a type of carbohydrate--beta-13-glucan in this case--along a larger carbohydrate molecule that makes a cell wall.
This could reduce insects'ability to transmit diseases to humans and animals. It may also lead to new biocontrol of pest insects as exploiting the mechanism could weaken
There are fungal pathogens that are used to kill insect pests but that are harmless to humans Kanost said.
If we understand how insect immune response fights off fungal infections that might lead to better ways to use microbial control on the insects.
just as effective as invasive neck surgery for long-term prevention of fatal and disabling strokes reports an international trial led by UCL (University college London) funded by the Medical Research Council and Stroke Association.
The research paper published today in the Lancet was authored by researchers from UCL Basel University Switzerland the London School of Hygiene & Tropical Medicine the University Medical center Utrecht Netherlands Sheffield Teaching Hospitals
Carotid artery disease occurs when cholesterol and fatty deposits build up in these arteries restricting blood flow
In the UK carotid artery disease is treated most commonly by an invasive surgical procedure called endarterectomy. Patients are put under general
or local anaesthetic and surgeons cut open the affected artery to remove the build up and then sew the wound up.
The operation leaves a scar on the neck and can lead to heart attack short-term facial paralysis from nerve damage and bleeding
The procedure is less invasive causing only minor bruising in the groin no risk of nerve damage and a lower heart attack risk than endarterectomy.
The study followed 1713 patients with carotid artery disease of whom 855 were assigned to stenting and 858 to endarterectomy for up to 10 years.
At the moment stenting is used not widely in the UK due to historical uncertainty over its long-term effectiveness says study leader Professor Martin Brown from the UCL Institute of Neurology.
A transient ischaemic attack also known as a mini-stroke can be a warning sign that someone has carotid artery stenosis
Preventative procedures to treat such carotid artery stenosis are therefore crucial. Carotid endarterectomy is a common yet invasive surgery used to treat carotid artery stenosis
and is used widely throughout the UK. Previously far less was known about the long-term effectiveness of stenting as an alternative procedure.
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