| To: HerbVic who wrote (7105) | 10/6/2015 2:55:02 AM | | From: loparn | | | | Thank you for the input. As I understand it Foxy-5 could be the first administered effective drug overall in directly inhibiting cancer cells from leaving a newly diagnosed primary tumor, travelling to the blodstream and invading another organ and thus substantially reduce the risk for metastasis to develop.
Foxy-5 does this by mimicking the natural protein Wnt-5a which inhibits up to 6 such different (downstream) mechanism in breast cancer. It has been preclinically shown in vitro in detail for breast cancer how this works and there are in vivo studies supporting that the antimetastatic effect occurs and that a high Wnt-5a-expression clinically correlates to a significantly longer diseasefree life.
The downstream antimetastatic mechanisms of Wnt-5a differ to a degree in colon and prostate cancer.
I think the doctors will love this medicine i.e. if WntResearch (and or a future Big Pharma partner) succeeds, and hopefully millions of cancer patients will as well.
The CEO of WntResearch professor Nils Brünner is very optimistic about Foxy-5.
So is the "brain" behind Foxy-5 the WntResearch CSO professor Tommy Andersson.
But there is of course always a risk in drug development... |
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| From: loparn | 10/14/2015 11:23:19 AM | | | | | | Swedish WntResearch has gained over 15 % in three days, starting the big move. My blogg was published at Redeye today :
redeye.se
WNT.ST has still an extremely fine risk/reward as the possibly first "antimetastatic drug company"
finance.yahoo.com
WntResearch will present their "exiting" results in Boston Nov 6. |
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| From: tnsaf | 11/7/2015 12:34:45 AM | | | | | | Microbes Play Role in Anti-Tumor Response
Gut microbiome composition can influence the effectiveness of cancer immunotherapy in mice.
By Anna Azvolinsky | November 5, 2015
The presence of certain types of gut microbes in mice can boost the anti-tumor effects of cancer immunotherapy, according to two studies from independent research teams published today (November 5) in Science Express.
Cancer immunotherapies that block immune inhibitory pathways are now available as treatments for several tumor types, yet patients’ responses to these therapies vary. Aside from the presence of T cells within the tumor before the start of treatment, it has not been clear what other factors are linked to a response to these antibodies. The two studies published today, while not the first to suggest that gut microbes can influence the efficacy of cancer therapy, provide a definitive link between gut microbiome composition and cancer immunotherapy response and implicate the positive role of specific bacterial species.
Emphasis added. The text of the article is at
http://www.the-scientist.com//?articles.view/articleNo/44418/title/Microbes-Play-Role-in-Anti-Tumor-Response/ |
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| From: IRWIN JAMES FRANKEL | 11/7/2015 7:05:45 AM | | | | | | This is pretty neat:
news.wustl.edu
Study reveals new, potent way to boost immunity and fight viruses???
Findings aid antiviral drug discovery
October 19, 2015
By Julia Evangelou Strait
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Y. ZHANG, X. JIN
Infected with encephalomyocarditis virus, human cells dial up immune defenses, especially the interferon system. Many of this system’s components, including some newly discovered by researchers at Washington University School of Medicine in St. Louis, converge in cells that harbor the virus and work to interfere with viral replication.
Many viral infections, such as the common cold, cause mild illnesses that the body’s immune system eventually defeats. But when viruses cause severe disease, doctors have few options for effective treatment.
Studying mice with a variety of viral infections, scientists at Washington University School of Medicine? in St. Louis have demonstrated a way to dial up the body’s innate immune defenses while simultaneously attacking a protein that many viruses rely on to replicate.
The findings, published Oct. 19 in Nature Immunology, reveal previously unknown weapons in the body’s antiviral immune arsenal and provide guidelines for designing drugs that could be effective against a broad range of viruses. The strategy involves enhancing the body’s interferon signaling system, long understood to be a vital part of antiviral defenses.
“We’ve discovered a new component of the interferon system,” said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine. “It does something that other components don’t do, and it works on both sides of the fence: It dials up the body’s internal genes that fight viruses, and it attacks viral proteins directly.”
Holtzman and lead author Yong Zhang, PhD, an instructor in pulmonary medicine, suspect that the researchers’ one-two punch against the virus may explain the large difference in survival rates between control mice and mice genetically engineered to have increased signaling in their interferon systems.??????????????
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When infected with encephalomyocarditis virus, which causes severe damage to vital organs including the brain, heart and pancreas, 97 percent of the genetically engineered mice survived, compared with none of the control mice. Even when the concentration of the injected virus was increased 100-fold, 82 percent of the genetically altered mice survived. And at 100-fold lower concentrations, all genetically engineered mice survived the infection, compared with only 25-28 percent of the control mice.
Holtzman pointed out that past research by other groups has shown that increasing the amount of interferon directly results in some improvements in fighting viruses, but not to the same extent as the current work. In addition, more modest improvements shown by other investigators usually are accompanied by autoimmune problems resulting from the chronically activated immune response. Despite the strong antiviral immune response seen in the new study, Holtzman and his colleagues reported no evidence of autoimmune disease in these mice.
Holtzman said a possible explanation for the impressive survival rates and absence of destructive autoimmunity could be that the researchers’ strategy did not involve increasing the amount of interferon, the first step of this important antiviral signaling cascade. Instead, it dialed up amounts of the protein STAT1, the second component of this cascade, without altering the system’s overall interferon on/off switch.
“Past work to boost this system just kept the interferon signal on all the time,” Holtzman said. “When the system is chronically activated, it is no longer regulated, and that’s where the autoimmune problems may come from. Our system is still regulated by the presence or absence of interferon. Interferon amounts increase when there is an infection and decrease when there is no infection. We’re not boosting interferon itself, but the secondary signal that interferon activates, which sets off the rest of the antiviral cascade. It’s like greasing the wheels. We’re not pushing the system any harder. But when we do push, we get a bigger effect.”
Analyzing the mice, the researchers found that the genetic alteration that confers these benefits turns on a set of molecules called PARP9-DTX3L. This molecular complex activates genes specifically designed to fight viruses. And, separate from its role in activating genes, the complex also seeks out and destroys an important viral protein called 3C protease, the scientists found. Many viruses including the common cold virus rely on this protein to replicate and continue their destructive march through the body.
“This dual mechanism of action is a great guideline for how we would like to build a new antiviral drug,” Holtzman said. “We want something that affects both host and virus. We already have drug candidates we can screen to see if they target this part of the system.”
Another potential advantage of this system, according to Holtzman, is that a drug with this dual function could be effective against different kinds of viruses that affect a variety of tissues, and especially those viruses that rely on 3C protease proteins for survival. In addition to testing mice with encephalomyocarditis virus, the researchers showed their system was effective in mice with equine encephalitis virus and with strains of influenza virus relevant to public health, including H5N1 and H1N1.
This work was supported by the Martin Schaeffer Fund and by the National Institutes of Health (NIH), grant numbers U19-AI070489, U54-AI05160, R01-AI111605, and R15-AI099134.
Zhang Y, Mao D, Roswit WT, Jin X, Patel AC, Patel DA, Agapov E, Wang Z, Tidwell RM, Atkinson JJ, Huang G, McCarthy R, Yu J, Yun NE, Paessler S, Lawson TG, Omattage NS, Brett TJ, Holtzman MJ. PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Nature Immunology. Oct. 19, 2015.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare. |
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| From: tnsaf | 11/9/2015 11:06:44 AM | | | | | | Ebola’s Immune Escape
The virus can persist in several tissues where the immune system is less active. Researchers are working to better understand this phenomenon and how it can stall the clearing of Ebola in survivors.
By Ashley P. Taylor | November 3, 2015
Even when a person has recovered from Ebola and his or her blood is Ebola-free, the virus can linger in the body. It can remain in semen for months after the initial infection. Late last year, it was found replicating in the eye of Ebola survivor Ian Crozier, an American physician who helped treat patients in Sierra Leone, nine weeks after he recovered from the illness. It has been detected in swabs of the bodies, amniotic fluid, and placentas of stillborn babies whose mothers were infected with and recovered from Ebola while pregnant, said Daniel Bausch, an emerging pathogens expert at Tulane University in New Orleans who worked with the World Health Organization (WHO) during the ongoing Ebola epidemic. Most recently, the virus has been detected in the nervous system of Scottish nurse Pauline Cafferkey, who recovered from Ebola about a year ago, but last month became very ill and developed meningitis—an inflammation of the membranes around the brain and spinal cord—noted Bausch, who consulted on the case.
A commonality among these cases is that they involve the recurrence of Ebola in sites where the immune system is known to be less active—sites of immune privilege. Immune privilege helps protect tissues in which, for various reasons, an immune response could be harmful. Sites of immune privilege include the placenta, the testes, the eye, and the brain.
Doctors have hypothesized that, after a person recovers from an Ebola infection, the virus can hide away in these immune-privileged sites and—as in the cases of Crozier and Cafferkey—later flare up. In such instances, especially when the infected person could not have been infected a second time, “the only possible way that we could surmise that the virus could be present is that it was seeded from the acute original infection and persisted,” Bausch said. “We have very ample and increasing evidence that the virus can persist in some of these sites [of immune privilege],” he added.
Help and harm
The immune system, meant to protect the body, can sometimes cause it harm. In the delicate tissues of the brain and eye, infection-related inflammation could do serious damage, said Boston University’s Andrew Taylor, who studies immune regulation and suppression in the eye. Once damaged, tissues of the eye can be slow to heal, and scarring can impede vision.
Meanwhile, immune privilege of the testes and placenta seems to keep the immune system from destroying the body’s own cells. Before birth, T cells go through a selection process whereby those that recognize antigens of their own body are eliminated. Because this process occurs during infanthood and sperm are not produced until puberty, the immune system considers these gametes foreign and, given the chance, may destroy them, explained Mark Hedger, a reproductive immunologist at the Hudson Institute of Medical Research in Melbourne, Australia.
Immune privilege of the placenta serves a similar purpose. Because the fetus contains genetic contributions from the father, “if the immune system were to detect that, it would actually attack the developing baby,” said Jannette Dufour of the Texas Tech University Health Sciences Center. Instead, “the immune response is controlled so that you can basically allow for development,” she explained. Immune privilege is thought to be a primarily mammalian phenomenon, Dufour said—one that mammalian reproduction depends on.
Probing the mechanism
Immune privilege involves three general components: a structural barrier between the blood, which carries immune cells, and the immune-privileged tissue; the production of immunosuppressive molecules; and the conversion of immune cells that could mount an immune response into ones that keep the immune system in check, explained Hedger.
In the testes, for example, sperm begin their lives in and around a network of tubes, called seminiferous tubules, lined by what are called Sertoli cells. The Sertoli cells are connected by tight junctions that let no cells or molecules through—except the developing germ cells—forming a blood-testis barrier. These undifferentiated germ cells, called spermatogonia, begin outside the Sertoli cells; then, as they develop into sperm, they pass through the Sertoli-cell barrier and move toward the center of the tubule.
Yet these tight junctions alone are not enough to protect developing germ cells, which form outside the blood-testis barrier, where immune cell-rich blood flows, said Hedger. A second layer of protection is provided by molecules produced by Sertoli cells, such as prostaglandins, which destroy activated T cells that could otherwise mount an immune response. As a third means of protection, molecules secreted by testicular cells, such as TGF-ß, help convert immune cells—both T cells and macrophages—from those that could spur an immune response to those that are immunoregulatory.
Similar mechanisms of immune suppression also exist in the brain, the eye, and the placenta, said Taylor. “The only difference that I can think [of] is that each immune-privileged tissue has a different set of cells . . . that are actually making the factors—the cells that are regulating the immune response,” he said. “The end result comes out the same.”
Another source of variation among immune-privileged sites lies in their structural barriers, said Dufour. The blood-brain barrier exists at the level of the blood vessel, which has tight junctions in its epithelium. Testicular blood vessels, on the other hand, do not have tight junctions; the blood-testis barrier is formed instead by the tight junctions of the Sertoli cells, she explained.
That a system set up to protect the body from its own immune system can serve as a hideout for Ebola may be distressing; however, in the study of Ebola persistence in semen, the frequency of Ebola-positive samples decreased with time. These and other data suggest that the body eventually defeats the pathogen.
“It’s just that these are sites where it’s harder for your immune system to get into and so it takes longer for it to get cleared,” said Bausch. “Over time, we do think that everyone who survives Ebola will be completely Ebola-free.”
Meanwhile, the WHO recommends that Ebola survivors abstain from sex or use condoms until their semen has twice tested negative for Ebola.
the-scientist.com |
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| From: tnsaf | 11/9/2015 10:26:32 PM | | | | | | Sunnybrook doctor first to perform blood-brain barrier procedure using focused ultrasound waves
WENCY LEUNG
The Globe and Mail
theglobeandmail.com
Published Sunday, Nov. 08, 2015 10:02PM EST
Last updated Monday, Nov. 09, 2015 2:49PM EST
Dr. Todd Mainprize leaned over and peered through his wire-rim glasses at a computer screen showing the brain scan of his brain cancer patient, Bonny Hall, who lay in a magnetic resonance imaging machine (MRI) in the adjacent room.
“This has gone exactly the way we hoped,” the neurosurgeon said, crossing his arms.
He smiled and nodded. His experimental procedure had been a success.
Here in the S-wing of Toronto’s Sunnybrook Hospital, Mainprize and his research team accomplished on Thursday what no one in the world has ever done before: Using focused ultrasound waves, they have opened the human blood-brain barrier, paving the way for future treatment of an array of currently impossible or hard-to cure-illnesses – from brain cancer to certain forms of depression, stroke, Parkinson’s disease and Alzheimer’s disease.
The blood-brain barrier is an extremely selective filter that Mainprize likens to cling film, which coats the blood vessels in the brain, preventing harmful substances in the bloodstream from passing through. Though its function is to protect the brain, this barrier has limited doctors’ ability to treat diseases, such as tumours, using drugs like chemotherapy to target specific areas of the brain.
By successfully opening the blood-brain barrier, “that will allow us to use many, many more medications in the brain than we can currently use,” said Dr. Kullervo Hynynen, director of physical sciences at Sunnybrook Health Sciences Centre, who developed the technology used in the experimental procedure.
Hynynen said about 98 per cent of molecules that could potentially be used for brain treatments cannot currently be used because they cannot get through the blood-brain barrier. This includes antibodies, which in animal studies have been shown to remove brain plaques involved in Alzheimer’s disease, or stem cells, which could be used to treat stroke patients. Thus, he says, the ability to penetrate the blood-brain barrier will “revolutionize” brain medicine.
Previous methods of circumventing this cling film-like coating have been inconsistent and difficult to control, or invasive, such as inserting microcatheters through the skull to inject drugs directly into the brain. But by using focused ultrasound, the Toronto researchers have demonstrated a way of breaching the blood-brain barrier that is non-invasive, selective (or contained within a specific area), reversible and, the researchers believe, safe.
Here’s how it works: Medication is first introduced into a patient’s bloodstream – in this case, a chemotherapy drug called liposomal doxorubicin. Next, microbubbles, or tiny air bubbles, which are typically used as a contrast medium to enhance visibility in ultrasound imaging, are intravenously delivered into the bloodstream. Using MRI to locate their target area, doctors then send focused ultrasound waves, causing the microbubbles in the brain’s capillaries to expand and contract. This expansion and contraction creates little tears in the cling film-like layer of endothelial cells of the blood-brain barrier, allowing the drug molecules to pass through into the brain to the targeted areas.
The microbubbles themselves do not cross the barrier and disappear within minutes, passing through the lungs. Meanwhile, the tiny tears in the blood-brain barrier close up again between an estimated eight to 12 hours.
The appearance of bright spots, the size of pinkie fingerprints, on the MRI images of Bonny Hall’s brain allowed Mainprize to immediately see that he had accomplished what he set out to do.
“This white spot and this white spot is where we opened the blood-brain barrier,” he said, pointing to the computer screen.
In the days previous, Hall, 56, of Tiny, Ont., was anxious yet eager to be the first patient to undergo the procedure.
“I think that someone has to go first,” Hall said, noting she empathized with the first patient to be treated with penicillin. “I kind of feel that way.”
Hall discovered her brain tumour eight years ago, though doctors at the time found it was benign. About five months ago, however, they found it had become cancerous and had grown to about five centimetres by three centimetres – about the size of a miniature candy bar – on the right side of her head, just above her ear.
Although the tumour caused no pain, Hall experienced what she described as “little blips,” or small 10– to 20-second seizures during which she would feel “spaced out.”
On the morning of the procedure, as the chemotherapy drug dripped into her arm, Hall said she was looking forward to getting her life back to normal.
“Seeing people here really suffer,” she said of the other patients at the hospital’s cancer centre, “I really do hope this will work for them some day.”
The following morning, after determining it possible to open the blood-brain barrier, Mainprize performed traditional surgery to remove Hall’s tumour. He carefully cut open a hand-sized flap of skin and muscle and removed part of her skull, extracting a white mass of tissue. The tumour will be analyzed over the next week to determine how much of the chemotherapy effectively passed through the blood-brain barrier.
The next step for the research team will be to repeat the focused ultrasound procedure on nine additional patients to show it can be replicated safely.
The possibilities for future research, Mainprize said, are enormous. “With ... this technique, you can selectively open almost anywhere in the brain and deliver whatever you want,” he said. “Essentially, whatever you can think of is a potential study that may help in the future.”
Follow Wency Leung on Twitter: @wencyleung |
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| From: Biotech Jim | 12/9/2015 7:56:55 AM | | | | | | Cara Therapeutics Announces Positive Top-Line Results From Phase 2a Trial of Oral CR845 in Chronic Pain Patients With Osteoarthritis of the Knee or Hip
>Dose-related reduction observed in mean baseline pain score up to 34 percent after two weeks, with statistically significant reduction in mean rescue medication for top 5.0 mg dose
>All four tablet strengths observed to be safe and well tolerated
>Establishes therapeutic doses and dosing regimen for Phase 2b trial in 2016
>Conference call today at 8:30 a.m. ET
http://ir.caratherapeutics.com/releasedetail.cfm?ReleaseID=946233
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| To: Biotech Jim who wrote (7112) | 12/30/2015 2:47:49 PM | | From: tuck | | | | RE: CARA Hey, BJ. Scoping the chart, I see this splattered in late September, but can see no news to cause the drop. Looks like they are executing on their plan and the drugs are performing well so far. Curious.
TIA & CHeers, Tuck |
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| To: tuck who wrote (7113) | 12/31/2015 9:17:03 AM | | From: Biotech Jim | | | | My recollection is that was during the general biotech turmoil. I continue to like CARA's chances.
Best wishes and the best of health for the New Year. |
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