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FDA approves a number of breakthrough therapies, including Cystic Fibrosis and cancer drugs

FDA approves a number of breakthrough therapies, including Cystic Fibrosis and cancer drugs | Amazing Science |

Two cystic fibrosis drugs have gained the first breakthrough therapy designation from the US Food and Drug Administration (FDA). In January, the agency announced that Vertex's Kalydeco (ivacaftor) alone and in combination with the experimental compound VX-809 would be the first to benefit from an expedited review process designed for potentially lifesaving drugs. In March, FDA added two oncology drugs to this pathway: the experimental lymphoma drug ibrutinib from Pharmacyclics of Sunnyvale, CA, and the Novartis drug LDK378 for the treatment of lung cancer. All three companies appear delighted but cautious about what the FDA breakthrough designation will mean for their products. FDA is considering another initiative, the Generating Antibiotic Incentives Now (GAIN) pathway, as an alternative approval for unmet medical needs, which appears to be intended mainly for anti-microbial drugs.

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Ingestible, Implantable, Or Intimate Contact: How Will You Take Your Microscale Body Sensors?

Ingestible, Implantable, Or Intimate Contact: How Will You Take Your Microscale Body Sensors? | Amazing Science |

Computer chips and silicon micromachines are ready for your body. It’s time to decide how you’ll take them: implantable, ingestible, or intimate contact. Every flavor now exists. Some have FDA approval and some are seeking it. Others are moving quickly out of the research lab stage. With the round one Qualcomm Tricorder X-Prize entries due in one year, we’re soon to see a heavy dose of sensors tied to the mobile wireless health revolution.


With these sensors comes a heavy dose of information about your health, data about what medication you are taking and when you took it. The sensors are available to protect your health, but choosing how to use them and how to protect the privacy of your data will be a matter of personal responsibility.



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Genetic Scientists Eliminate Schizophrenia Symptoms in Mice by Targeting Neuregulin-1 (NRG1)

Genetic Scientists Eliminate Schizophrenia Symptoms in Mice by Targeting Neuregulin-1 (NRG1) | Amazing Science |

Geneticists writing in the journal Neuron reversed schizophrenia-like symptoms in adult mice by restoring normal expression to the gene Neuregulin-1 (NRG1).


Targeting expression of NRG1, which makes a protein important for brain development, may hold promise for treating at least some patients with the brain disorder. Like patients with schizophrenia, adult mice biogenetically-engineered to have higher NRG1 levels showed reduced activity of the brain messenger chemicals glutamate and γ-aminobutyric acid (GABA). The mice also showed behaviors related to aspects of the human illness.

“They genetically engineered mice so they could turn up levels of NRG1 to mimic high levels found in some patients then return levels to normal,” explained senior author Dr Lin Mei from the Medical College of Georgia at Georgia Regents University.


“They found that when elevated, mice were hyperactive, couldn’t remember what they had just learned and couldn’t ignore distracting background or white noise. When they returned NRG1levels to normal in adult mice, the schizophrenia-like symptoms went away.”


While schizophrenia is generally considered a developmental disease that surfaces in early adulthood, the team found that even when they kept NRG1 levels normal until adulthood, mice still exhibited schizophrenia-like symptoms once higher levels were expressed. Without intervention, they developed symptoms at about the same age humans do.


“This shows that high levels of NRG1 are a cause of schizophrenia, at least in mice, because when you turn them down, the behavior deficit disappears,” Dr Mei said. “Our data certainly suggests that we can treat this cause by bringing down excessive levels of NRG1 or blocking its pathologic effects.”


“Schizophrenia is a spectrum disorder with multiple causes – most of which are unknown – that tends to run in families, and high NRG1 levels have been found in only a minority of patients. To reduce NRG1 levels in those individuals likely would require development of small molecules that could, for example, block the gene’s signaling pathways,” Dr Mei said.


“Current therapies treat symptoms and generally focus on reducing the activity of two neurotransmitters since the bottom line is excessive communication between neurons.”


The good news is it’s relatively easy to measure NRG1 since blood levels appear to correlate well with brain levels. To genetically alter the mice, the scientists put a copy of the NRG1 gene into mouse DNA then, to make sure they could control the levels, they put in front of the DNA a binding protein for doxycycline, a stable analogue for the antibiotic tetracycline, which is infamous for staining the teeth of fetuses and babies. The mice are born expressing high levels of NRG1 and giving the antibiotic restores normal levels.


“If you don’t feed the mice tetracycline, the NRG1 levels are always high. Endogenous levels of the gene are not affected. High-levels of NRG1 appear to activate the kinase LIMK1, impairing release of the neurotransmitter glutamate and normal behavior. The LIMK1 connection identifies another target for intervention,” Dr Mei concluded.

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3-Year Search Uncovers Novel Hemorrhagic Fever Virus

3-Year Search Uncovers Novel Hemorrhagic Fever Virus | Amazing Science |

Ebola virus, Marburg virus, Lassa fever, Rift Valley fever, yellow fever, and dengue are well known viruses from four different viral families that can cause hemorrhagic fever. But an international team of researchers report in PLoS Pathogens today that the rhabdovirus family, which typically causes brain swelling or flulike disease, can join the club of hemorrhagic fever agents, which are among the most virulent pathogens known to humans.


Using sophisticated RNA sequencing technology, the researchers discovered evidence that links a rhabdovirus to acute hemorrhagic fever in three people from the village of Mangala between 25 May and 14 June 2009. The first two people afflicted with the frightening disease died. But a third, a male nurse who treated both patients at a health center, survived.


The researchers did not actually isolate a rhabdovirus, but instead plucked out RNA sequences from the surviving man's blood sample and reconstructed what they contend is the genome of the pathogen that caused the disease. "It looks fairly solid," says Thomas Ksiazek, an epidemiologist and virologist who specializes in hemorrhagic disease at the University of Texas Medical Branch in Galveston. "Clearly, they have identified a virus in one of the three patients they describe. But trying to make more out of this is speculative. Is the disease due to the agent? You can speculate all you want, but until you have a virus in hand it's hard to answer that."


Delwart's group randomly amplified genetic material with the polymerase chain reaction, sequenced the products, and then checked what they created against databases of known genomes. "We got one very intriguing read," Delwart says. "It was clearly a rhabdovirus." But his team couldn't amplify any more meaningful sequence, so they passed the sample on to Charles Chiu, head of a viral discovery center at the University of California, San Francisco. Chiu sequenced 140 million fragments of genetic material and then merged related fragments to assemble the genome of the Bas-Congo virus.


Virologist Joseph Fair, who works with Metabiota, says the researchers could not isolate the actual virus because it took so long for the nurse's sample to arrive at a lab that could probe for agents. "We do the best we can with what we have here," Fair says, speaking by phone from Isiro, Congo, where he's working on a new Ebola outbreak. "We're trying to build capacity to build cold chains in cases like this."


Fair points to several lines of evidence that the Bas-Congo virus is real. He notes that the research teams exhaustively searched for other pathogens. "We found nothing except this rhabdovirus," he emphasizes. Based on genomic copies of Bas-Congo virus, the nurse also had high levels of the bug. The researchers then made a lab tool known as a pseudovirus, which contained the surface protein from Bas-Congo inside of a vesicular stomatitis virus, to run a confirmatory antibody test.


Specifically, they showed that antibodies taken from the nurse in January 2012, as well as from an asymptomatic nurse who cared for him, prevented the pseudovirus from infecting cells in a culture dish. Fair and his co-authors also note that another hemorrhagic fever virus, Lujo, was first found in 2009 using similar genetic techniques to those they relied on.


But Fair acknowledges the importance of isolating the virus itself. "Since we weren't able to get an isolate, that limits what we can know about how it kills people and the effect it has on the immune system," Fair says. "Along with our Congolese colleagues, our next step will be to mount an expedition to find this virus."

CineversityTV's curator insight, May 28, 2013 6:22 AM

what we predicted 4 years ago is starting to SARS found also..AIRBORNE VIRUS..

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Scientists discover the molecular trigger for the sensation of itch and itch response

Scientists discover the molecular trigger for the sensation of itch and itch response | Amazing Science |

Neuroscientists Mark Hoon and Santosh Mishra of the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, searched for the molecule that encodes the sensation of itch by screening genes in sensory neurons that are activated by touch, heat, pain and itch. They found that one particular protein, called natriuretic polypeptide b, or Nppb, was expressed in only a subset of these neurons.


Mutant mice lacking Nppb did not respond to itch-inducing compounds, but did respond normally to heat and pain. The researchers also found that when they injected Nppb in the mice's necks, it put them into a self-scratching frenzy. This occurred both in the mutants and in control mice.

“Our research reveals the primary transmitter used by itch sensory neurons and confirms that itch is detected by specialized sensory neurons,” says Hoon.

Hoon and Mishra went on to find neurons bearing receptors for Nppb in the spinal cord. Injection of a toxin made from soapwort seeds that targeted these spinal-cord neurons blocked itch responses, but not other sensory responses, suggesting that information about the itch sensation is transmitted along a distinct pathway.


The result “explains problems in the literature and provides a very testable hypothesis for how itch works”, says Glenn Giesler, a neuroscientist at the University of Minnesota in Minneapolis.


Previous research suggested that gastrin-releasing peptide, or GRP, was the neurotransmitter released by sensory neurons to initiate itch-related signals. But Hoon and Mishra, as well as another group of researchers, failed to find GRP outside the spinal cord, indicating that GRP is not the primary trigger.


However, Hoon and Mishra found that GRP is still involved in the itch response. Injecting GRP into mice lacking either Nppb or its receptor produced strong scratching responses. Also, mice in which GRP receptors were inhibited did not engage in scratching behaviour, even with spinal-cord injection of Nppb. These results place GRP-releasing neurons downstream of Nppb in the transmission of the itch sensation.

“This model fits better with what everyone else is seeing,” says Sarah Ross, a neuroscientist at the University of Pittsburgh in Pennsylvania.

The neural pathways for itch in humans are similar, though not identical, to those in mice, and it is unknown whether they involve Nppb or something similar to it, Hoon says. He adds that he plans to follow up with human studies later on.


Giesler says that itch is a common problem, being associated with more than two dozen conditions, including eczema and psoriasis. “Antihistamines work for a few forms of itch, but for the vast majority they do nothing,” he says. “This research introduces a brand new target for clinical treatment.”

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Scientists identify cells that could hold the secret to limb regeneration

Scientists identify cells that could hold the secret to limb regeneration | Amazing Science |

The failure to replace damaged body parts in adult mammals results from a muted growth response and fibrotic scarring. Although infiltrating immune cells play a major role in determining the variable outcome of mammalian wound repair, little is known about the modulation of immune cell signaling in efficiently regenerating species such as the salamander, which can regrow complete body structures as adults. A comprehensive analysis of immune signaling during limb regeneration in axolotl, an aquatic salamander, revealed a temporally defined requirement for macrophage infiltration in the regenerative process. Although many features of mammalian cytokine/chemokine signaling are retained in the axolotl, they are more dynamically deployed, with simultaneous induction of inflammatory and anti-inflammatory markers within the first 24 h after limb amputation. Systemic macrophage depletion during this period resulted in wound closure but permanent failure of limb regeneration, associated with extensive fibrosis and disregulation of extracellular matrix component gene expression. Full limb regenerative capacity of failed stumps was restored by reamputation once endogenous macrophage populations had been replenished. Promotion of a regeneration-permissive environment by identification of macrophage-derived therapeutic molecules may therefore aid in the regeneration of damaged body parts in adult mammals.

Salamanders are unique in the vertebrate world as they're capable of repairing their hearts, tails, spinal cords, brain, and regrowing limbs. This makes them an obvious candidate for regenerative research. Godwin and the team at ARMI removed the macrophages the Salamanders and found that the animals were no longer able to regenerate limbs. He believes that the cells release chemicals that are vital to the Salamanders' regenerative powers. More research is needed to establish exactly how regeneration works, and Godwin is currently conducting experiments to investigate. "This really gives us somewhere to look for what might be secreted into the wound environment that allows for regeneration," he says.


Although understanding the Salamander's abilities may one day lead to impossible-sounding feats like limb regeneration in humans, there are more-immediate benefits that could come from the research. Less ambitious goals such as scarless healing, could be attainable. "The long-term plan is that we'll know exactly what cocktail to add to a wound site to allow salamander-like regeneration under hospital conditions."

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87% cut in asthma attacks reported in mid-stage drug trial - drug seen as potential game changer

87% cut in asthma attacks reported in mid-stage drug trial - drug seen as potential game changer | Amazing Science |

A new type of asthma drug meant to attack the underlying causes of the respiratory disease slashed episodes by 87 percent in a mid-stage trial, making it a potential game changer for patients with moderate to severe disease, researchers said on Tuesday.

"Overall, these are the most exciting data we've seen in asthma in 20 years," said Dr. Sally Wenzel, lead investigator for the 104-patient study of dupilumab, an injectable treatment being developed by Regeneron Pharmaceuticals Inc and French drugmaker Sanofi.


The drug also met all its secondary goals, such as improving symptoms and lung function and reducing the need for standard drugs called beta agonists.


Although far larger trials will be needed to confirm findings from the "proof of concept" study, researchers expressed optimism. They noted that dupilumab has also shown the ability to tame atopic dermatitis, or severe eczema, an allergic condition that is not well controlled by current treatments.


Results of the 12-week asthma study are being presented on Tuesday at the annual scientific meeting of the American Thoracic Society in Philadelphia.


The medicine, if approved, could hold promise for patients with moderate to severe persistent asthma that is not well controlled by standard drugs.


"We have been treating asthma with sort of Band-Aid therapies that didn't get at the underlying causes," Wenzel said in an interview, adding that dupilumab could be an important step in going to the root of the problem.

The drug works by simultaneously blocking proteins that have been linked to inflammation, interleukin-4 (IL-4) and interleukin-13 (IL-13).

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41 of 43 patients with HIV stay healthy for over 11 years after initial gene therapy, T-cells perpetuate & persist

41 of 43 patients with HIV stay healthy for over 11 years after initial gene therapy, T-cells perpetuate & persist | Amazing Science |

HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.


"We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T cells in their bodies."


Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, allay that concern in T cells, further buoying the hope generated by work June's team published in 2011 showing the eradication of tumors in patients with chronic lymphocytic leukemia using a similar strategy.


"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.


They also note that the approach the Penn Medicine team studied may allow patients with cancers and other diseases to avoid the complications and mortality risks associated with more conventional treatments, since patients treated with the modified T cells did not require drugs to weaken their own immune systems in order for the modified cells to proliferate in their bodies after infusion, as is customary for cancer patients who receive stem cell transplants.

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Goodbye smallpox vaccination, hello monkeypox

Goodbye smallpox vaccination, hello monkeypox | Amazing Science |

In 8 May 1980, the World Health Organisation declared that “the world and its peoples are free from smallpox.” Through decades of intense vaccination, this once fatal disease had been wiped out. It was a singular victory and having won it, countries around the world discontinued the vaccination programmes. After all, why protect against a disease that no longer exists, except in a few isolated stocks?


Unfortunately, this is not a rhetorical question. The smallpox vaccine did more than protect against smallpox. It also reduced the risk of contracting a related illness called monkeypox, which produces the same combination of scabby bumps and fever. It’s milder than smallpox but it’s still a serious affliction. In Africa, where monkeypox originates from, it kills anywhere from 1-10% of those who are infected. And more and more people are becoming infected.


Anne Rimoin from the University of California, Los Angeles compared data on the virus in the Democratic Republic of Congo over the last three decades. She found that, during those years, monkeypox has become 20 times more common in humans. In one particular area, 72 people out of every million were infected each year between 1981 and 1986. Between 2005 and 2007, that figure rose to 1442 per million. Rimoin thinks that we eased up the pressure on smallpox vaccination too soon. Between 1981 and 1985, only 404 cases turned up in all of Africa, and simulations predicted that the disease was unlikely to spread too far in a human population before dying out. This was no public health threat. In 1986, even the monitoring programme was stopped. In 2005 however, Rimoin’s group, together with the DRC Ministry of Health and the World Health Organization set up a new round of monkeypox surveillance and they spent two years collecting data. Their research showed that the disease is gaining ground.


Rimoin found that monkeypox was disproportionately affecting children and almost all of those who fell sick were born after 1980, when the smallpox vaccination programme was halted in the DRC. The vaccine wasn’t a perfect defence against monkeypox but it was still around 85% effective. Among people who were born during the vaccination era, those who were immunised were 5 times less likely to develop monkeypox than their protected peers. And this protection is clearly long-lasting; even 25 years on, they could still ward off the related virus.


These figures are probably underestimates too. The region’s inconsistent healthcare isn’t exactly conducive to accurate disease monitoring and Rimoin says that her team had word of many more cases, but couldn’t always check them out because of their remote location.


Monkeypox is spread by animals including squirrels and, fairly obviously, monkeys. As humans encroach upon the DRC’s tropical rainforests, the risk of being exposed to an infected carrier grows. Indeed, Rimoin found that the odds of contracting monkeypox were higher for people living near forested areas, and for men. As civil strife continues to affect the DRC, locals are being forced to rely more on hunting to get enough food and that brings men in close contact with furry viral reservoirs.


It’s an emerging threat, but Rimoin isn’t calling for smallpox vaccination to resume. Doing so would be logistically difficult in an area where even collecting data can be fraught. It might be better to take a more targeted approach, vaccinating only health workers who treat infected patients, and people who come into frequent contact with animal carriers. It may also be worth educating local people about the dangers of handling carrier species and the benefits of isolating people who show the very obvious symptoms, until they can be treated.


But most importantly, Rimoin wants active surveillance in regions where the virus circulates, especially since there are still so many unknowns about the virus. We need to better understand how it moves from human to human (and from animal to human), how often it’s fatal, or what the complications are.


It’s a good opportunity to take action now, at a time when the monkeypox is still confined to specific areas. Things might not stay that way. In 2003, there was a bizarre outbreak in the United States, as rodents from Ghana brought the disease to American prairie dogs, who handed it over to humans. All sorts of rodents the world over might become reservoirs for the disease and Rimoin writes, “If monkeypox were to become established in a wildlife reservoir outside Africa, the public health setback would be difficult to reverse.”

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Fighting cancer by taking cells that normally attack common infections and targeting cancer instead

Fighting cancer by taking cells that normally attack common infections and targeting cancer instead | Amazing Science |

‘Hijacking’ cells that normally attack common infections to target cancer instead could offer the body a ready-made army against the killer disease University researchers and Oxford-based biotech company, Immunocore Limited have uncovered.


The Immunocore team engineered a range of TCRs to bind very tightly to cancer cells and equipped them with the ability to activate non-cancer specific T cells. This new class of drug, named ‘ImmTACs’ (Immune Mobilising mTCR against Cancer), can be used to ‘hi-jack’ the body’s existing T cells that normally kill viruses and redirect them to kill cancer cells instead.


The team included Nat Liddy and Katy Adams, Immunocore employees and PhD students at Cardiff University, as well as Professors Andy Sewell and David Price, School of Medicine.


Nat Liddy said: "With Immuncore’s novel ImmTAC drugs we found we could effectively target cancer cells and mark them for destruction by the killer T cells that might normally fight common infections.


"Our initial studies and findings show that administration of ImmTAC could, potentially, result in the regression of established tumours". The Immunocore team engineered a range of TCRs to bind very tightly to cancer cells and equipped them with the ability to activate non-cancer specific T cells. Recent advances have enabled molecular targeting of disease using immune molecules called antigen receptors. There are two main classes of antigen receptor: antibodies and T cell receptors.


Therapeutic application of antibodies has been a huge medical success over the last decade and over 40% of the new drugs on the market in 2011 were based on these molecules. Exploitation of T cell receptors (TCRs) has so far lagged behind, but research led by Immunocore Ltd, with help from Cardiff University’s Institute of Infection and Immunity, is set to close the gap and open up an entirely new field of medical treatments.


Professor Andy Sewell, School of Medicine, said: "T cell receptors have advantages over antibodies as these molecules can see inside cells and tell if they are abnormal. Similar technology based around antibodies has shown great promise in clinical trials. This new TCR-based research technology extends this potential as it could possibly be applied to any form of cancer."


The most advanced of Immunocore’s ImmTACs, a drug called IMCgp100, is already in clinical trials in the UK and US for the treatment of melanoma. A second oncology ImmTAC, IMCmage1, is set to enter the clinic in both countries later this year and is applicable to the treatment of a large number of poorly served cancer indications.


James Noble, Immunocore’s CEO, said: "The power of this new technology lies in its ability to be used for a host of cancers that are currently very difficult to treat. We look forward to building on the emerging clinical data and generating a robust pipeline of products over the coming years".

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Discovery of new hormone opens doors to new type 2 diabetes treatments

Discovery of new hormone opens doors to new type 2 diabetes treatments | Amazing Science |
Researchers have discovered that a particular type of protein (hormone) found in fat cells helps regulate how glucose (blood sugar) is controlled and metabolized in the liver.


Harvard School of Public Health (HSPH) researchers have discovered that a particular type of protein (hormone) found in fat cells helps regulate how glucose (blood sugar) is controlled and metabolized (used for energy) in the liver. Using experimental models and state-of-the-art technology, the scientists found that switching off this protein leads to better control of glucose production from the liver, revealing a potential new target that may be used to treat type 2 diabetes and other metabolic diseases.

The study appears online in the May 7, 2013 issue of Cell Metabolism.

"Although it has long been recognized that a key event leading to development of type 2 diabetes is uncontrolled glucose production from the liver, underlying mechanisms have been elusive," said senior author Gökhan S. Hotamisligil, chair of the Department of Genetics and Complex Diseases and J.S. Simmons Professor of Genetics and Metabolism at HSPH. "We now have identified aP2 as a novel hormone released from fat cells that controls this critical function."


The ability of one organ -- in this case, the adipose tissue -- to so directly and profoundly control the actions of another -- the liver -- is in itself very exciting, said Hotamisligil. "We suspect this communication system between adipose tissue and liver may have evolved to help fat cells command the liver to supply the body with glucose in times of nutrient deprivation. However, when the engorged fat cells lose control over this signal in obesity, the blood levels of aP2 rise, glucose is poured into the bloodstream and cannot be cleared by other tissues. The result is high blood glucose levels and type 2 diabetes."

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Double Mastectomy: What We Know About BRCA Mutations and Breast Cancer

Double Mastectomy: What We Know About BRCA Mutations and Breast Cancer | Amazing Science |

Angelina Jolie decided to go for a double mastectomy. She doesn’t have cancer yet, but like many women with breast cancer mutations, she had the radical surgery to lower her risk.


Describing her decision as “My Medical Choice,” the 37-year-old actress revealed in an op-ed in the New York Times that she carries the BRCA1 gene mutation, which gives her an 87% risk of developing breast cancer at some point in her life. The abnormal gene also increases her risk of getting ovarian cancer, a typically aggressive disease, by 50%. To counteract those odds, Jolie wrote that she decided to have both her breasts removed.


While radical, her decision to pre-empt any future cancer is a common one, and backed by studies. In 2010, Australian scientists found that women with the BRCA1 or BRCA2 mutations who chose to have preventive mastectomies did not develop breast cancer over the three-year follow-up. What’s more, since the genetic abnormalities increase the risk of ovarian cancer, women who had their ovaries and fallopian tubes removed also dramatically lowered their risk of developing ovarian or breast cancers. They were 89% less likely to develop ovarian cancer and 61% less likely to develop breast cancer over three years than their counterparts who did not have prophylactic surgery. Among the 250 study participants who underwent preventive mastectomies, none developed breast cancer during the study follow-up. Additionally, a patient’s surgical choice affected overall mortality rates, both cancer related and not: only 3 percent of surgery participants died at the time of the study follow-up versus 10 percent of those who avoided the surgery.


And while the mutations are inherited – a mother with either aberration has a 50-50 chance of passing it on to her children – women who don’t get the mutation are not at increased risk of developing breast cancer, even if they belong to families with a history of the disease. Previous studies had suggested that women who did not have the mutations but had a mother or sister who did, could have up to a five times greater risk of developing different types of breast cancer, which led them to schedule frequent biopsies and even preventive mastectomies. The latest research, however, suggests that’s not necessarily the case.


But the new study counters those findings, concluding that the risk of breast cancer in women from BRCA families, who do not carry the mutations themselves, are no higher than that of women in families with other types of breast cancer. The study involved more than 3,000 families with breast cancer, including nearly 300 who had the BRCA1 or BRCA2 mutations.


The genetic test for the BRCA mutations isn’t done for every woman, or even for every woman who is at risk of developing breast cancer. Doctors recommend it for those who develop cancer at a young age, or have multiple family members with the disease. It’s expensive – up to $3000 – and insurers require that patients meet a threshold for needing the test before they cover its cost. Jolie is fortunate to be able to afford not just the test but the reconstructive surgery following the procedure as well. But she’s aware that not all women are even aware of the genetic screening and may not be able to afford the testing. She wrote that her goal in announcing her choice to remove her breasts prophylactically is to raise awareness of the test and the treatment options that women have if they are positive for the mutations.

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Researchers Identify 4 New Genetic Risk Factors For Testicular Cancer

Researchers Identify 4 New Genetic Risk Factors For Testicular Cancer | Amazing Science |

Tapping into three genome-wide association studies (GWAS), the researchers, including Peter A. Kanetsky, PhD, MPH, an associate professor in the department of Biostatistics and Epidemiology, analyzed 931 affected individuals and 1,975 controls and confirmed the results in an additional 3,211 men with cancer and 7,591 controls. The meta-analysis revealed that testicular germ cell tumor (TGCT) risk was significantly associated with markers at four loci—4q22, 7q22, 16q22.3, and 17q22, none of which have been identified in other cancers. Additionally, these loci pose a higher risk than the vast majority of other loci identified for some common cancers, such as breast and prostate.


This brings the number of genomic regions associated with testicular cancer up to 17—including eight new ones reported in another study in this issue of Nature Genetics.


Testicular cancer is relatively rare; however, incidence rates have doubled in the past 40 years. It is also highly heritable. If a man has a father or son with testicular cancer, he has a four-to six-fold higher risk of developing it compared to a man with no family history. That increases to an eight-to 10-fold higher risk if the man has a brother with testicular cancer.

Given this, researchers continue to investigate genetic variants and their association with cancer.


In 2009, Dr. Nathanson and colleagues uncovered variation around two genes—KITLG and SPRY4—found to be associated with an increased risk of testicular cancer. The two variants were the first striking genetic risk factors found for this disease at the time. Since then, several more variants have been discovered, but only through single GWAS studies.


"This analysis is the first to bring several groups of data together to identify loci associated with disease," said Dr. Nathanson, "and represent the power of combining multiple GWAS to better identify genetic risk factors that failed to reach genome-wide significance in single studies."

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Gene therapies for regenerative surgery are getting closer

Gene therapies for regenerative surgery are getting closer | Amazing Science |

Experimental genetic techniques may one day provideplastic and reconstructive surgeons with an invaluable tool—the ability to promote growth of the patient’s own tissues for reconstructive surgery.


A review of recent progress toward developing effective gene therapies for use in regenerative surgery appears in the June issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).


Over the past ten years, researchers have developed several promising gene therapy techniques to grow skin, bone, and other tissues for reconstructive surgery. But they still face many challenges in developing gene-based approaches that can make the leap from the research lab to the operating room, according to the review by Dr. Giorgio Giatsidis and colleagues of Padua University Hospital, Italy.


Dr. Giatsidis and coauthors reviewed the state of the art in research on gene therapy techniques for treatment of local disorders and injuries—the first such review in more than a decade. They found studies using gene therapy to promote the growth of “almost every different tissue” for use in regenerative surgery. “Gene therapy may represent a leading strategy to develop more efficient regenerative surgical treatments for numerous clinical needs,” they write.

Gene therapy has the potential to provide reconstructive surgeons with a new approach to solving one of their most difficult problems: the lack of adequate tissues to correct deformities of a specific area or structure. For example, in patients with relatively small burns, plastic and reconstructive surgeons have designed a wide range of skin flaps for use in transferring healthy tissue to the burned area.


But for patients with burns involving larger areas, the lack of suitable tissues for coverage may severely limit the reconstructive options. Using gene techniques to promote growth of specific types of tissues would be a major step forward in the ability to perform truly regenerative surgery.


Several research groups are pursuing gene therapy approaches to regenerate skin, such as using genes to control expression of growth factors involved in skin healing. One small study reported promising results with tissue-engineered products to promote healing of diabetic skin ulcers.


Researchers are also targeting growth factors involved in new bone formation, with promising results in techniques using transplantation of genetically modified donor bone. One study reported clinical benefits using gene therapy to regenerate joint cartilage in patients with rheumatoid arthritis. Techniques to promote healing of tendons, regeneration of injured nerves, and growth of skin flaps for reconstructive surgery are all being explored.

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Stem cell injections improve spinal injuries in rats

Stem cell injections improve spinal injuries in rats | Amazing Science |

A single injection of human neural stem cells produced neuronal regeneration and improvement of function and mobility in rats impaired by an acute spinal cord injury (SCI), an international team led by researchers at the University of California, San Diego School of Medicine reports.


Grafting neural stem cells derived from a human fetal spinal cord to the rats’ spinal injury site produced an array of therapeutic benefits — from less muscle spasticity to new connections between the injected stem cells and surviving host neurons.



Via Ray and Terry's
AnalyticalInstrument's curator insight, May 29, 2013 2:49 PM

Can we get them to test them on rat knees?

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Bizarre 6-Inch Skeleton Shown to Be Human

Bizarre 6-Inch Skeleton Shown to Be Human | Amazing Science |

Subhuman primate? Deformed child? Mummified fetus? The Internet is buzzing over the nature of "Ata," a bizarre 6-inch-long skeleton featured in a new documentary on UFOs. A Stanford University scientist who boldly entered the fray has now put to rest doubts about what species Ata belongs to. But the mystery is not over.


The story began 10 years ago, when the diminutive remains were reportedly found in a pouch in a ghost town in the Atacama Desert of Chile. Ata ended up in a private collection in Barcelona; producers of the film Sirius latched onto the bizarre mummy as evidence of alien life.

Last fall, immunologist Garry Nolan, director of the National Heart, Lung, and Blood Institute's Proteomics Center for Systems Immunology at Stanford in California, heard about Ata from a friend and contacted the filmmakers, offering to give them a scientific readout on the specimen. They asked him to give it a shot.


Among the apparent abnormalities, Ata sports 10 ribs instead of the usual 12 and a severely misshapen skull. "I asked our neonatal care unit how you would go about analyzing it. Had they seen this kind of syndrome before?" Nolan says. He was directed to pediatric radiologist Ralph Lachman, co-director of the International Skeletal Dysplasia Registry at Cedars-Sinai Medical Center in Los Angeles, California. "He literally wrote the book on pediatric bone disorders," Nolan says. Lachman was blown away, Nolan recalls: "He said, 'Wow, this is like nothing I've ever seen before.' "


To study the specimen, Nolan sought clues in Ata's genome. He initially presumed the specimen was tens or hundreds of thousands of years old—the Atacama Desert may be the driest spot on the planet, so Ata could have been preserved for eons. He consulted experts who had extracted DNA from bones of the Denisovans, an Asian relative of European Stone Age Neandertals. It turned out that their protocols weren't necessary. "The DNA was modern, abundant, and high quality," he says, indicating that the specimen is probably a few decades old.


To the chagrin of UFO hunters, Ata is decidedly of this world. After mapping more than 500 million reads to a reference human genome, equating to 17.7-fold coverage of the genome, Nolan concluded that Ata "is human, there's no doubt about it." Moreover, the specimen's B2 haplotype—a category of mitochondrial DNA—reveals that its mother was from the west coast of South America: Chile, that is.


Meanwhile, after examining x-rays, Lachman concluded that Aka's skeletal development, based on the density of the epiphyseal plates of the knees (growth plates at the end of long bones found only in children), surprisingly appears to be equivalent to that of a 6- to 8-year-old child. If that holds up, there are two possibilities, Nolan says. One, a long shot, is that Ata had a severe form of dwarfism, was actually born as a tiny human, and lived until that calendar age. To test that hypothesis, he will try to extract hemoglobin from the specimen's bone marrow and compare the relative amounts of fetal versus adult hemoglobin proteins. The second possibility is that Ata, the size of a 22-week-old fetus, suffered from a severe form of a rare rapid aging disease, progeria, and died in the womb or after premature birth.


Nolan hasn't yet turned up hits for genes known to be associated with progeria or dwarfism. He's stepping up the search for mutations through additional sequencing and casting a wider net. Another possibility is a teratogen: a birth defect-inducing toxicant along the lines of thalidomide. Nolan plans to analyze tissue using mass spectrometry to look for toxicants or metabolites. But reports of a handful of other Tom Thumb-sized skeletons from Russia and elsewhere have Nolan leaning toward a genetic explanation.


At least one expert has a more prosaic take—but agrees that the specimen is human. "This looks to me like a badly desiccated and mummified human fetus or premature stillbirth," says William Jungers, a paleoanthropologist and anatomist at Stony Brook University Medical Center in New York. He notes that "barely ossified and immature elements" of the hands and feet, and the wide open metopic suture, where the two frontal bones of the skull come together down the middle of the forehead. "Genetic anomalies are not evident, probably because there aren't any," he says. Nolan responds that the rib number and epiphyseal plate densities remain a riddle; while he is open to the fetus hypothesis, he thinks that the jury is still out.


Nolan's analysis went viral this week; besieged as he has been by the media circus, he doesn't regret having gotten involved in debunking a claim of alien life. "I'm thrilled with the outcome," he says. Once the analyses are complete, he says, he'll submit his findings for peer review. The other claim Nolan debunks is that Ata is an elaborate hoax. The x-rays clearly show these are real bones, complete with arterial shadows, he says. "You just couldn't fake it," he says, adding, with a laugh, "unless you were an alien."

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RNA Interference: Nanocoatings on bandages could deliver RNAs to shut off disease-related genes

RNA Interference: Nanocoatings on bandages could deliver RNAs to shut off disease-related genes | Amazing Science |

Medical researchers think specially tailored RNA sequences could turn off genes in patients’ cells to encourage wound healing or to kill tumor cells. Now researchers have developed a nanocoating for bandages that could deliver these fragile gene-silencing RNAs right where they’re needed (ACS Nano 2013, DOI:10.1021/nn401011n). The team hopes to produce a bandage that shuts down genes standing in the way of healing in chronic wounds.


Small interfering RNAs, or siRNAs, derail expression of specific genes in cells by binding to other RNA molecules that contain the code for those genes. Biologists have developed siRNAs that target disease-related genes. But for these siRNAs to reach the clinic, researchers must find a way to deliver the molecules safely to the right cells. Unfortunately, free oligonucleotides like siRNAs don’t fare well inside the body or cells as enzymes and acids quickly chop them up, says Paula T. Hammond, a chemical engineer at Massachusetts Institute of Technology.


Other groups have tackled this delivery challenge by attaching siRNAs to chemical carriers that protect the oligonucleotides as they travel through the bloodstream. The pharmaceutical company Sanofi-Aventis asked Hammond to design a vehicle that would work at the site of a wound or tumor, releasing the siRNAs over a long period of time. The company hoped that putting the biomolecules right where they’re needed, without them having to survive a trip through the bloodstream, would increase the efficacy of the treatment.


Hammond and her colleagues produced an siRNA-containing nanocoating that could be applied to a wide range of medical materials, such as bandages or biodegradable polymers doctors could implant during surgery to prevent an excised tumor from coming back. As the coating slowly dissolves, it releases siRNA molecules tethered to protective nanoparticles.


The thin films consist of two different materials: a peptide called protamine sulfate and calcium phosphate nanoparticles decorated with the therapeutic siRNAs. Other researchers have shown that similar nanoparticles help the nucleotides evade destruction once they’re taken up by cells (J. Controlled Release 2010, DOI: 10.1016/j.jconrel.2009.11.008).


The team alternately dips whatever they want to coat in water solutions of the two materials. The RNA and nanoparticles are negatively charged, and the peptides are positively charged. The two substances cling together due to electrostatic force, producing a film when the water dries.


To test their delivery method, the researchers coated woven nylon bandages with 80-nm-thick films and applied the bandages to layers of human and animal cells in culture. In one experiment, a bandage loaded with 19 µg of siRNA per square centimeter released two-thirds of its load over 10 days. Other bandages made using siRNAs targeting the gene for fluorescent green protein almost completely shut down the protein’s production in cells expressing the gene. Hammond says the group is now testing bandages that knock down MMP9, a collagen-destroying protein associated with slow healing in chronic wounds.

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Baby's life saved with groundbreaking 3D printed device that restored his breathing

Bioresorbable splint used for first time, successfully stopped life-threatening tracheobronchomalacia.


Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions weren’t true.


“Quite a few doctors said he had a good chance of not leaving the hospital alive,” says April Gionfriddo, about her now 20-month-old son, Kaiba. “At that point, we were desperate. Anything that would work, we would take it and run with it.”


They found hope at the University of Michigan, where a new, bioresorbable device that could help Kaiba was under development.  Kaiba’s doctors contacted Glenn Green, M.D., associate professor of pediatric otolaryngology at the University of Michigan.


His colleague, Scott Hollister, Ph.D., professor of biomedical engineering and mechanical engineering and associate professor of surgery at U-M, went right into action, obtaining emergency clearance from the Food and Drug Administration to create and implant a tracheal splint for Kaiba made from a biopolymer called polycaprolactone.


On February 9, 2012, the specially-designed splint was placed in Kaiba at C.S. Mott Children’s Hospital. The splint was sewn around Kaiba’s airway to expand the bronchus and give it a skeleton to aid proper growth. Over about three years, the splint will be reabsorbed by the body. The case is featured today in the New England Journal of Medicine.


“It was amazing. As soon as the splint was put in, the lungs started going up and down for the first time and we knew he was going to be OK,” says Green.


Green and Hollister were able to make the custom-designed, custom-fabricated device using high-resolution imaging and computer-aided design. The device was created directly from a CT scan of Kaiba's trachea/bronchus, integrating an image-based computer model with laser-based 3D printing to produce the splint.

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Scientists prevent heart failure in mice

Scientists prevent heart failure in mice | Amazing Science |

Cardiac stress, for example a heart attack or high blood pressure, frequently leads to pathological heart growth and subsequently to heart failure. Two tiny RNA molecules play a key role in this detrimental development in mice, as researchers at the Hannover Medical School and the Göttingen Max Planck Institute for Biophysical Chemistry have now discovered. When they inhibited one of those two specific molecules, they were able to protect the rodent against pathological heart growth and failure. With these findings, the scientists hope to be able to develop therapeutic approaches that can protect humans against heart failure.


The scientists involved in this study had observed that these microRNAs are more prevalent in the cardiac muscle cells of mice suffering from cardiac hypertrophy. To determine the role that the two microRNAs play, the scientists bred genetically modified mice that had an abnormally large number of these molecules in their heart muscle cells. "These rodents developed cardiac hypertrophy and lived for only three to six months, whereas their healthy conspecifics had a normal healthy life-span of several years," explained Kamal Chowdhury, researcher in the Department of Molecular Cell Biology at the Max Planck Institute for Biophysical Chemistry. "For comparison, we also selectively switched off these microRNAs in other mice. These animals had a slightly smaller heart than their healthy conspecifics, but did not differ from them in behaviour or life-span," continued the biologist. The crucial point is when the scientists subjected the hearts of these mice to stress by narrowing the aorta, the mice did not develop cardiac hypertrophy – in contrast to normal mice.


The scientists were also able to protect normal mice against the disease. When they gave them a substance that selectively inhibits microRNA-132, no pathological cardiac growth occurred – even when the hearts of these mice were subjected to stress. "Thus, for the first time ever, we have found a molecular approach for treating pathological cardiac growth and heart failure in mice," said the cardiologist Thomas Thum, MD, Director of the Institute for Molecular and Translational Therapy Strategies (IMTTS) at the Hannover Medical School. With these findings, the researchers hope that they will be able to develop therapeutic approaches that can also protect humans against heart failure. "Such microRNA inhibitors, alone or in combination with conventional treatments, could represent a promising new therapeutic approach," said Thum.


"In mice with an overdosage of the two microRNAs in their heart muscle cells, the cellular ‘recycling program' is curbed," explained Ahmet Ucar, who together with Shashi K. Gupta was responsible for the experiments. In this recycling process, the cell breaks down components that are damaged or no longer required and reuses their constituents – a vital process that, for example, ensures the organism’s survival under stress conditions. In mice without the microRNAs -212 and 132, this recycling program is more active than in their normal conspecifics. Conceivably, the reduced cellular recycling could be a cause of the observed cardiac hypertrophy. 

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Number of obese Americans to climb to 42% by 2030, CDC finds and could cost $550 billion over 20 years

Number of obese Americans to climb to 42% by 2030, CDC finds and could cost $550 billion over 20 years | Amazing Science |

A whopping 42% of Americans will be obese by 2030, and the swelling ranks of the rotund could end up costing the nation hundreds of billions of dollars. The scary statistics are revealed in a study released Monday by the Centers for Disease Control and Prevention.


Currently more than a third of Americans are obese and the number is rising, particularly in men and the elderly. Buried in the CDC’s research is a nugget of good news. Even though the number of obese Americans continues to go up, it’s starting to go up at a slower rate.


The slowdown is a small victory in the fight for better health. Were obesity to rise at the same rapid rate it has in the last two decades, half the U.S. population would be obese by 2030, the study found.


The CDC’s study looked at the ramifications of the obesity crisis, including its economic impact. If the problem isn't curbed, it could cost the country $550 billion in health care costs over the next 20 years, researchers found.

Obesity — defined as a Body Mass Index over 30 — can lead to diabetes, heart disease and other serious health problems. And 27% of the rise in medical costs over the last 30 years can be pinned to excess weight, researchers wrote in the American Journal of Preventive Medicine. Even tiny progress in preventing obesity-related health conditions would save millions of dollars in health care costs, researchers wrote.


The Institute of Medicine, a nonprofit health organization, released national strategies for combating obesity Tuesday on its website, such as making nutritious foods more widely available and promoting health in schools and the workplace.


The study is based on BMI data collected by the CDC and state health departments from 1990 through 2008 as part of the Behavioral Risk Factor Surveillance System.

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3D ultrasound hologram printing service of unborn fetuses using Pioneer's compact holographic printer

A Japanese company, Pioneer, has unveiled a service that creates 3D holograms of unborn fetuses. Ultrasound photos - sooo old school from last century! Make way for hologram-babies. The service uses data gathered during a routine pregnancy checkup. The information from an echogram is used to create a 3D digital model of the baby on a computer. That digital model is then printed using Pioneer's compact hologram printer, first developed end of 2012. Within two hours, you have a stunning, but slightly creepy, multi-colored 3D image that lets you see your child from a range of angles.


Holograms are recordings of "light fields", the sum of the scattered light reflecting off a surface in a range of directions. (As opposed to an ordinary photograph, which captures only the light scattered in one direction). By capturing the light from a range of directions, the "light field", the hologram allows a 3D recreation of the original object. Creating a hologram from scratch is a straightforward but tricky process. (See our "How To" here). But the printer developed by Pioneer bypasses all of that, at least as far as you're concerned.


"Previously, holograms were produced by making a model of the subject, shining two lights on the model, and photographing it. That method involved a lot of work, because it required a darkroom, knowledge of techniques, and specialized equipment," said a spokesperson for Pioneer. "But with the device we've developed, even if you don't have the actual object, as long as you have a CG design, then that can be used to record a hologram easily."


Advances in holographic technology have seen holograms invade various areas of modern life. Researchers at Cambridge are investigating the security applications of holograms embedded in carbon nanotubes; it has been suggested that infrared holographic images could aid firefighters; and in 2012, Coachella festival in California featured a performance from a holographic Tupac -- though it wasn't a "hologram"in the strictest sense of the word.

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Elucidation of insulin “docking“ mechanism could lead to better diabetes treatments

Elucidation of insulin “docking“ mechanism could lead to better diabetes treatments | Amazing Science |

Despite decades of study, scientists remained unsure as to how insulin binds to the insulin receptor on the surface of cells to allow them to take up sugar from the blood and transform it into energy. Now, a definitive answer has now been found with a team of scientists capturing the first three-dimensional images of insulin “docking” to its receptor. It is hoped that the new knowledge can be exploited to develop new and improved insulin medications to treat type 1 and type 2 diabetes.


The international research team was led by scientists from the Walter and Eliza Hall Institute (WEHI) in Melbourne, with collaborators from La Trobe University, the University of Melbourne, Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague.


Using the MX2 microcrystallography beamline at Australia’s Synchrotron, the researchers were able to obtain highly detailed, three-dimensional x-ray images of insulin and the insulin receptor to reveal how the two interact.


“We have now found that the insulin hormone engages its receptor in a very unusual way,” Associate Professor Mike Lawrence from the WEHI said. “Both insulin and its receptor undergo rearrangement as they interact – a piece of insulin folds out and key pieces within the receptor move to engage the insulin hormone. You might call it a 'molecular handshake'.”

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AT13148 - A Novel Oral Multi-AGC Kinase Inhibitor Has Potent Antitumor Activity

AT13148 - A Novel Oral Multi-AGC Kinase Inhibitor Has Potent Antitumor Activity | Amazing Science |

Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers. The simultaneous inhibition of multiple AGC kinases may increase antitumor activity and minimize clinical resistance compared with a single pathway component.


A research team from the UK investigated the detailed pharmacology and antitumor activity of the novel clinical drug candidate AT13148, an oral ATP-competitive multi-AGC kinase inhibitor. Gene expression microarray studies were undertaken to characterize the molecular mechanisms of action of AT13148.


Their results show that AT13148 caused a substantial blockade of AKT, p70S6K, PKA, ROCK, and SGK substrate phosphorylation and induced apoptosis in a concentration and time-dependent manner in cancer cells with clinically relevant genetic defects in vitro and in vivo. Antitumor efficacy in HER2-positive, PIK3CA-mutant BT474 breast, PTEN-deficient PC3 human prostate cancer, and PTEN-deficient MES-SA uterine tumor xenografts was shown. These experiments demonstrate for the first time that induction of AKT phosphorylation at serine 473 by AT13148, as reported for other ATP-competitive inhibitors of AKT, is not the therapeutically relevant reactivation step. Gene expression studies showed that AT13148 has a predominant effect on apoptosis genes, whereas the selective AKT inhibitor CCT128930 modulates cell-cycle genes. Induction of upstream regulators including IRS2 and PIK3IP1 as a result of compensatory feedback loops was observed.

Thus, the clinical candidate AT13148 is a novel oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity, which shows a distinct mechanism of action from other AKT inhibitors. AT13148 will now be assessed in a first-in-human phase I trial.

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New Skin Patch Warns People When It’s Time to Get Out of the Sun

New Skin Patch Warns People When It’s Time to Get Out of the Sun | Amazing Science |

By the time most of us realize we’ve been out in the sun too long, it’s too late. It can take up to 24 hours after exposure before you realize you have a sunburn.


Now, a Michigan Technological University Senior Design team has devised a sensor that tells you when it’s time to seek shelter, long before your skin gets red and tender.


The biomedical engineering seniors developed a skin patch imprinted with a graphic—in this case, a happy face design. The nickel-size patch gradually darkens under ultraviolet light, the type of light that causes sunburn and skin cancer.  When you can’t see the happy face anymore, it’s time to get out of the sun.


Not everyone burns at the same rate, and the team took that into account. “We calibrated it based on skin type,” said team member Anne François. Their prototypes were made for the three skin types that are most susceptible to sunburn.


The patch is made with UV-sensitive film bonded to a special tape with medical-grade adhesive that can withstand plenty of trips into the swimming pool. Because it measures total UV exposure, it “knows” when a user applies sunscreen or goes in the shade and darkens more slowly.

The team has filed a provisional patent on their invention and received Best Overall Award in the  Invention Disclosure Competition at Michigan Tech’s 2013 Undergraduate Expo. If it makes it to market, it would be inexpensive: the prototypes cost only 13 cents apiece in materials.

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Tumor-Activated Protein Promotes Cancer Metastases

Tumor-Activated Protein Promotes Cancer Metastases | Amazing Science |

Roughly 90 percent of all cancer deaths are due to metastasis – the disease spreading from the original tumor site to multiple, distant tissues and finally overwhelming the patient’s body. Lymph vessels are often the path of transmission, with circulating tumor cells lodging in the lymph nodes – organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.


The researchers, led by principal investigator Judith A. Varner, PhD, professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumors called VEGF-C activates a receptor called integrin α4β1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumor cells.


“One of the most significant features of this work is that it highlights the way that tumors can have long-range effects on other parts of the body, which can then impact tumor metastasis or growth,” said Varner.


Varner said α4β1 could prove to be a valuable biomarker for measuring cancer risk, since increased levels of the activated protein in lymph tissues is an indirect indicator that an undetected tumor may be nearby.


She said whole-body imaging scans of the lymphatic network might identify problem areas relatively quickly and effectively. “The idea is that a radiolabeled or otherwise labeled anti-integrin α4β1 antibody could be injected into the lymphatic circulation, and it would only bind to and highlight the lymphatic vessels that have been activated by the presence of a tumor.”


Varner noted that α4β1 levels correlate with metastasis – the higher the level, the greater the chance of the cancer spreading. With additional research and clinical studies, doctors could refine treatment protocols so that patients at higher risk are treated appropriately, but patients at lower or no risk of metastasis are not over-treated.


The researchers noted in their studies that it is possible to suppress tumor metastasis by reducing growth factor levels or by blocking activation of the α4β1 receptor. Varner said an antibody to VEGF-R3 is currently in Phase 1 clinical trials. An approved humanized anti-α4β1 antibody is currently approved for the treatment of multiple sclerosis and Crohn’s disease. Varner said her lab at UC San Diego Moores Cancer Center is investigating the possibility of developing one for treating cancer.

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