Silicon Investor - Biotech News

[DewDiligence_on_SI] Musing on AZN's counterintuitive COVID-19 data: investorshub.advfn.com

DewDiligence_on_SI — 11/23/2020 12:13:09 PM

[DewDiligence_on_SI] China has a health problem: investorshub.advfn.com

DewDiligence_on_SI — 6/24/2019 9:29:27 PM

[DewDiligence_on_SI] FDA approves NVS’ Mayzent* for MS—including SPMS: fda.gov a/k/a siponimod, B...

DewDiligence_on_SI — 3/26/2019 8:02:34 PM

FDA approves NVS’ Mayzent* for MS—including SPMS:

fda.gov

a/k/a siponimod, BAF312.

[DewDiligence_on_SI] Musings on RVNC's (shockingly cheap) valuation: investorshub.advfn.co...

DewDiligence_on_SI — 3/3/2019 8:59:16 PM

Musings on RVNC's (shockingly cheap) valuation: investorshub.advfn.com

[DewDiligence_on_SI] Corteva Caveat: twitter.com

DewDiligence_on_SI — 12/14/2018 11:34:38 AM

[DewDiligence_on_SI] RVNC's enterprise value is only $835M: investorshub.advfn.com

DewDiligence_on_SI — 11/3/2018 4:48:17 PM

[DewDiligence_on_SI] LLY spins off ~20% of Elanco: investorshub.advfn.com investorshub.advfn.com

DewDiligence_on_SI — 9/19/2018 7:55:40 PM

[LetsInvest] LexaGene Holdings Inc. (OTCQB:LXXGF (TSXV:LXG) Unveils a Revolutionary Pathogen ...

LetsInvest — 7/6/2018 9:37:20 AM

LexaGene Holdings Inc. (OTCQB:LXXGF (TSXV:LXG) Unveils a Revolutionary Pathogen Detection System

LexaGene Holdings Inc. (OTCQB: LXXGF) (TSX-V:LXG) has unveiled a first of its kind Pathogen detection technology capable of detecting a variety of pathogens including E.coli and Staph. According to the biotechnology company, the new prototype is far more effective than any other system in use, and should go a long way in reducing incidences of foodborne illness outbreaks.

LexaGene’s Technology Capabilities

The new technology is specifically designed for healthcare providers as well as food safety officers given that it is capable of is analyzing six samples at a time while searching for over 22 pathogens. Unlike in the past where healthcare officials had to send specimens far away and wait for days to get results, LexaGene’s new technology promises results in about an hour.

The technology will not only be used to reduce chances of shipping contaminated items in the food industry but also provide doctors an easy way of diagnosing sick patients. Carried out tests have shown that the technology can be relied upon to detect and identify the presence of antibiotic-resistant bacteria. Healthcare providers should thus be able to treat patients with more targeted therapies while still in healthcare facilities.

LexaGene’s technology is a much easier and less expensive solution for detecting deadly bacteria compared to other solutions in use at the moment. The company is planning to demonstrate capabilities of the new technology, which has shown to have the potential of revolutionizing a number of multibillion-dollar industries including food safety, water quality monitoring and veterinary diagnostics as well as aquaculture pathogen surveillance market.

“Over the next several months, we will continue to optimize the performance of the instrument and equip it with reagents to detect more diseases such as Salmonella and Listeria. Once we finalize our pathogen-detection panel, we’ll begin processing samples to demonstrate our advantages over standard testing procedures,” said CEO Jack Regan.

Strategic collaborations

In addition, Lexagene has entered into a collaboration agreement with Stanford University School of Medicine. Under the terms of the agreement, the biotechnology company is to leverage a targeted sequencing technology developed in the laboratory of Dr. Hanlee Ji in combination with its Microfluidic instruments.

Integration of the two technologies should expand LexaGene’s technology capabilities allowing it to include cancer diagnostics and Next Generation Sequencing. The biotechnology has been aggressive in signing deals with collaborators as it looks to refine and optimize the technology’s capabilities.

The company has already entered into agreements with Texas A&M Veterinary Medical Diagnostics Laboratory and Ethos Veterinary Health. The two are to supply the biotechnology company with Canine urine samples that are to be used for testing using the company’s LX6 prototype for more effective pathogen detection

The samples should go a long way in helping the company’s assays as well as optimize the LX6 prototype. Working with collaborators from different geographic regions should allow the company to gain access to adequate representation of diseases from different climates.

The biotechnology company remains confident that the technology will soon be the world’s first easy-to-use open access rapid pathogen detection system.

[Sultan] Antibe Therapeutics Releases Secondary Endpoint Data from Recent Phase 2B Gastro...

Sultan — 7/3/2018 1:22:18 PM

Antibe Therapeutics Releases Secondary Endpoint Data from Recent Phase 2B Gastrointestinal Safety Study for Lead Drug, ATB-346

finance.yahoo.com

[tnsaf] Diabetes Researchers Find Switch for Fatty Liver Disease Interesting article in ...

tnsaf — 5/23/2018 4:46:26 PM

Diabetes Researchers Find Switch for Fatty Liver Disease
Interesting article in DDD Magazine on this topic

Duke researchers have identified a key fork in the road for the way the liver deals with carbohydrates, fats and protein. They say it could be a promising new target for combating the pandemics of fatty liver disease and prediabetes.

dddmag.com

[DewDiligence_on_SI] RVNC apparently has the Botox cell line: investorshub.advfn.com

DewDiligence_on_SI — 3/18/2018 3:05:10 PM

[tnsaf] The garbage masquerading as information on websites can be quite humorous. For e...

tnsaf — 9/24/2017 6:06:30 PM

The garbage masquerading as information on websites can be quite humorous. For example, this one appears to combines a template with a database that fills in blanks, but some of the fields in the database are empty: economicsandmoney.com.

[DewDiligence_on_SI] ADXS (belatedly) shows AXAL/Durvalumab phase-2 data in cervical/H&N cancers: inv...

DewDiligence_on_SI — 8/23/2017 6:20:36 PM

ADXS (belatedly) shows AXAL/Durvalumab phase-2 data in cervical/H&N cancers: investorshub.advfn.com

[IRWIN JAMES FRANKEL] Healing wounds without scaring. Early animal study but interesting if it transl...

IRWIN JAMES FRANKEL — 5/22/2017 9:14:04 AM

Healing wounds without scaring. Early animal study but interesting if it translates to humans.

newscientist.com

[nigel bates] Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed...

nigel bates — 5/6/2017 8:30:38 AM

Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism
pnas.org

Abstract
Effective control of endotoxins and bacteria is crucial for normal wound healing. During injury, the key enzyme thrombin is formed, leading to generation of fibrin. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which bind to and form amorphous amyloid-like aggregates with both bacterial lipopolysaccharide (LPS) and gram-negative bacteria. In silico molecular modeling using atomic resolution and coarse-grained simulations corroborates our experimental observations, altogether indicating increased aggregation through LPS-mediated intermolecular contacts between clusters of TCP molecules. Upon bacterial aggregation, recombinantly produced TCPs induce permeabilization of Escherichia coli and phagocytic uptake. TCPs of about 11 kDa are present in acute wound fluids as well as in fibrin sloughs from patients with infected wounds. We noted aggregation and colocalization of LPS with TCPs in such fibrin material, which indicates the presence of TCP-LPS aggregates under physiological conditions. Apart from identifying a function of proteolyzed thrombin and its fragments, our findings provide an interesting link between the coagulation system, innate immunity, LPS scavenging, and protein aggregation/amyloid formation.

[nigel bates] RNA editing in coleoid cephalopods: theatlantic.com

nigel bates — 4/7/2017 6:54:40 AM

[idos] Sinclair is doing the Sirtris thing again?! time.com

idos — 3/25/2017 3:27:40 AM

[tnsaf] "The nervous and immune systems communicate and reciprocally influence their fun...

tnsaf — 1/30/2017 6:31:50 PM

"The nervous and immune systems communicate and reciprocally influence their functional responses. Nature Immunology and Nature Neuroscience team up to present a joint focus issue comprising of specially commissioned review articles that examine how the nervous system and immune cells interact during development, during homeostasis and in pathogenic disease states."

nature.com

[Miljenko Zuanic] BMY: Indeed...

Miljenko Zuanic — 1/30/2017 1:47:02 AM

BMY: <This makes a good buying opportunity for patient investors, IMO. >

Indeed, it is!

[DewDiligence_on_SI] Musings on BMY's 4Q16 results /2017 guidance: siliconinvestor.com

DewDiligence_on_SI — 1/26/2017 12:55:44 PM

[DewDiligence_on_SI] DARPA wants GM insects to deliver disease-fixing genes to food crops: technology...

DewDiligence_on_SI — 12/5/2016 10:45:39 AM

DARPA wants GM insects to deliver disease-fixing genes to food crops: technologyreview.com

[tom pope] theguardian.com

tom pope — 8/12/2016 10:11:59 AM

[tom pope] theguardian.com

tom pope — 8/11/2016 11:50:49 AM

[DewDiligence_on_SI] Botulinum toxin ought to work for that indication, IMO. Not sure how difficult t...

DewDiligence_on_SI — 8/7/2016 12:27:14 PM

Botulinum toxin ought to work for that indication, IMO. Not sure how difficult the clinical-trial program would be.

[tom pope] If it attacks essential tremor I'm a buyer

tom pope — 8/7/2016 12:23:09 PM

[DewDiligence_on_SI] RVNC has a mystery non-cosmetic indication to be announced when phase-2 starts. ...

DewDiligence_on_SI — 8/7/2016 11:17:35 AM

RVNC has a mystery non-cosmetic indication to be announced when phase-2 starts.

What is it?

siliconinvestor.com

siliconinvestor.com

[DewDiligence_on_SI] BMY/MRK—Musings on CHECKMATE-026 study: siliconinvestor.com

DewDiligence_on_SI — 8/6/2016 1:20:03 PM

[tnsaf] Pinpointing How New Drugs Exert Beneficial Effects Wed, 07/06/2016 - 8:22amby Co...

tnsaf — 7/8/2016 11:48:34 AM

Pinpointing How New Drugs Exert Beneficial Effects
Wed, 07/06/2016 - 8:22amby Cold Spring Harbor Laboratory

A collaborative effort by cancer researchers at Cold Spring Harbor Laboratory (CSHL) and chemists at Boehringer Ingelheim (BI), a pharmaceutical firm, has resulted in the identification of a new drug target in leukemia and creation of a candidate drug that hits the target. Perhaps even more important, the research demonstrates a new, highly accurate way of proving how this and certain other classes of drugs work -- extremely valuable information in the risky business of drug development. The research appears today in Nature Chemical Biology.

The cancer in question is a particularly aggressive form of blood cancer called acute myeloid leukemia, or AML, which is often fatal. The newly identified target is a binding pocket on a protein called BRD9. The drug designed by BI to bind at that pocket, called a bromodomain, is provisionally called BI-7273.

The team of academic and industry scientists, led by Associate Professor Christopher Vakoc of CSHL in coordination with Dr. Manfred Koegl of BI, identified BRD9 in screens, then demonstrated its importance in human AML cells grown in culture and in rodent models of AML.

Like nearly all proteins, BRD9 is subdivided into sections called domains, each of which has a specific function. Each domain is encoded by a portion of the BRD9 gene. The domain of interest to Dr. Anja Hohmann, first author of the new paper who performed the research while still a graduate student in Vakoc's lab, was BRD9's bromodomain, the subunit of the protein that "reads" chromatin, a bundled form of the cell's genetic material.

[Full article...] dddmag.com

[DewDiligence_on_SI] RVNC opportunity has parallels to buying ENTA (in the teens) in mid-2013: silico...

DewDiligence_on_SI — 1/18/2016 6:27:12 PM

RVNC opportunity has parallels to buying ENTA (in the teens) in mid-2013: siliconinvestor.com

[Biotech Jim] My recollection is that was during the general biotech turmoil. I continue to l...

Biotech Jim — 12/31/2015 9:17:03 AM

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.

[tuck] RE: CARA Hey, BJ. Scoping the chart, I see this splattered in late September...

tuck — 12/30/2015 2:47:49 PM

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

[Biotech Jim] Cara Therapeutics Announces Positive Top-Line Results From Phase 2a Trial of Ora...

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

[tnsaf] Sunnybrook doctor first to perform blood-brain barrier procedure using focused u...

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

[tnsaf] Ebola’s Immune Escape The virus can persist in several tissues where the immune ...

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

[IRWIN JAMES FRANKEL] This is pretty neat: news.wustl.edu Study reveals new, potent way to boost imm...

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
Print Forward Facebook this Tweet this Share more

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.??????????????

Follow the School of Medicine
Facebook @WUSTLmed Google+

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.

[tnsaf] Microbes Play Role in Anti-Tumor Response Gut microbiome composition can influen...

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/

[loparn] Swedish WntResearch has gained over 15 % in three days, starting the big move. M...

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.

[loparn] Thank you for the input. As I understand it Foxy-5 could be the first administer...

loparn — 10/6/2015 2:55:02 AM

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...

[HerbVic] … Metastasis is now responsible for around 90 % of the deaths in cancer but ther...

HerbVic — 10/5/2015 9:49:29 PM

… Metastasis is now responsible for around 90 % of the deaths in cancer but there are no available drugs now in the market focusing on preventing metastasis. Foxy-5 may be the first.

…

Maybe the first produced by a drug company. I'm not so sure you can say that inclusive of Mother Nature. While there are no double blind studies, some doctors have reported anecdotal evidence that breast and prostate cancers can both be prevented and reversed if treated early with hormone balancing in principal, in practice progesterone supplementation. The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females. - Progesterone - Wikipedia. The drug companies don't have any skin in that treatment, though. Molecules found in nature can't be patented.

In the U.S., the medical industry first became aware of this avenue of treatment back when it was discovered in 1974 that a deficiency of the 5a reductase enzyme and DHT was the etiology behind a genetic mutation that produced male children with ambiguous sexual characteristics who had underdeveloped prostates after becoming adults. Finasteride (brand names Proscar, and Propecia by Merck) a 5a reductase inhibitor, was later developed by Merck for treatment of benign prostate hyperplasia and approved in 1992. It appears that no real attempt has been made to find and treat what may be the cause or trigger of excess 5a reductase in older men, which brings me to the reason for my post, my light hearted but heartfelt little rant.

Today's medical establishment is much more interested in treatment [for life] than they are in cause discovery and remediation. That's understandable when it comes to drug companies. It is somewhat disheartening when it comes to doctors. But, doctors are courted heavily by the drug companies and prescribing drugs is the mainstay of the MD's professional practice. After all, MD means Doctor of Medicine. Find a man you can cure, and you'll eat for a day. Find a man you can treat for life and you'll feed your whole family from now on.

To save myself from writing a very long winded explanation, here's a link to some very interesting explanations of the links between hormonal imbalance and prostate hyperplasia as well as evidence that breast cancer and prostate cancer are really the same disease with the same etiology.

growyouthful.com

[loparn] The Swedish biotech company WntResearch will present their clinical Phase I-stud...

loparn — 10/5/2015 4:17:46 PM

The Swedish biotech company WntResearch will present their clinical Phase I-study results at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston Nov 6.
The WntResearch drug candidate Foxy-5 has emerged as a possible new blockbuster in a novel cancer treatment concept targeting the lethal metastatic process by agonising the Wnt-5a signalling pathway in breast, colon and prostate cancer. There are at least 36 scientific studies supporting Foxy-5/Wnt-5a in these cancer forms.
Metastasis is now responsible for around 90 % of the deaths in cancer but there are no available drugs now in the market focusing on preventing metastasis. Foxy-5 may be the first.

The Phase I results will include several different biomarkers for antimetastatic effect and possibly two biomarkers for anticancerstemcell effect in breast, colon and prostate cancer. Circulating tumor cells, which are an indication of metastatic disease, in the blood have also been measured before and after treatment with Foxy-5.

I and my PdD wife have analyzed the scientific studies concerning Wnt-5a and the Wnt-5a-mimicking small molecule hexapeptide Foxy-5 carefully and found them very very promising indicating a paradigm shift in the treatment of metastatic cancer to become likely within a few years.
The internal and external preclinical work are very impressing in vitro, in vivo and importantly with clinical favorably survival data connected to high Wnt-5a expression in the primary tumors of breast, colon and prostate cancers.
Both Wnt-5a and its (and Foxy-5's) receptor Frizzled-5 are highly conserved between mice and cancer patients, reducing the risk for failure.
No side effects have been reported to the market in the as of September terminated Phase I study. Normally Wnt-5a probably has its most fundamental significance on the embryonal level.
We who have followed WntResearch closely the last few years are also "calmed" by our CEO who is a professor and very experienced cancer researcher and who has made many statements and clues for at least half a year that cannot be interpreted as negative, rather quite the opposite...

The WNT.ST stock may explode the next month when the results of the biomarkers become official.
My fundamentally based valuation now of WntResearch is an incredible over 20 times the current stock price on the Swedish small "Aktietorget" market. Aktietorget has probably several bad stocks, but at least one likely gem. Aktietorget is connected to NASDAQ OMX Stockholm.
The WntResearch market value is around USD 100 million, but a takeover could occur at some 20-40 times that figure considering the Phase I breast cancer oriented Seragon buyout by Roche in 2014.

I have made a rather short english version of the very, very long swedish analysis of WntResearch, which can be reached by this link : infoom.se

WntResearch's own official presentation of the Foxy-5 project can be found here :
wntresearch.com

To analyze WntResearch should be of great value to biotech investors seeking an extremely attractive risk/reward in my opinion.

[Arthur Radley] Steven Brill and this Huffington article does an excellent job recounting the re...

Arthur Radley — 9/27/2015 11:20:37 PM

Steven Brill and this Huffington article does an excellent job recounting the recent J&J lawsuit---Huffington post a new chapter every day so one has to start at the beginning to understand how this case played out in a Philly court.

highline.huffingtonpost.com

[Jibacoa] According to the NIH the SPRINT trial shows that the goal or target for BP level...

Jibacoa — 9/11/2015 10:55:57 AM

According to the NIH the SPRINT trial shows that the goal or target for BP levels,
in hypertensives should be around 120mms Hg and not 140 as previously thought. <g>
nih.gov

Bernard

[Jibacoa] O.T. Neither was I. As a matter of fact, I always try to smile. Even on d...

Jibacoa — 8/28/2015 10:16:45 AM

O.T.

Neither was I.<g>
As a matter of fact, I always try to smile.<g>
Even on days when I have lost more than a couple of hundred Ks,
since they have made me not to forget to keep a a proper protective stop loss.<g>

I always respect Peter's opinions, even when he is speaking ex-cathedra,
which in this case you said he was not.<g>
However, opinions keep changing over time, remember how many people thought the earth was flat,
and that the Pope excomulgated Copernicus when he said the Earth revolved around the Sun. <g>

And in the computerized environment that we now live, opinions keep changing at a much faster pace.<g>

RAGL,

Bernard

[tom pope] I was not being serious, and in any event Peter was not speaking ex cathedra.

tom pope — 8/28/2015 9:39:18 AM

[Jibacoa] O.T. Yes, he may have enunciated that principle some years ago, but now a day...

Jibacoa — 8/28/2015 9:13:44 AM

O.T.

Yes, he may have enunciated that principle some years ago,
but now a days important things are happening on a daily basis,
and you can't depend on principles that the erudites were enunciating that far back.<g>

Most Bostonians and people from other States up North, are not aware of the present exodus from
States like New York and California into Florida and Texas, or the reasons for it.<g>

Bernard

[tom pope] I think it was Peter who years ago enunciated the principle that Biotechs with F...

tom pope — 8/27/2015 10:14:26 PM

I think it was Peter who years ago enunciated the principle that Biotechs with Florida addresses were to be shunned.

[Jibacoa] Well it seems that the people at Jacksonville are making some progress. Wit...

Jibacoa — 8/27/2015 5:26:52 PM

Well it seems that the people at Jacksonville are making some progress.<g>
With new research going on at Jupiter, Orlando, Jacksonville, Gainesville and other places,
it seems Florida is starting to compete with other States. <g>

New Cancer Research at Mayo Clinic (in Jacksonville):
newsnetwork.mayoclinic.org

Bernard

[IRWIN JAMES FRANKEL] sciencedaily.com Researchers identify nerve-guiding protein that aids pancreati...

IRWIN JAMES FRANKEL — 8/23/2015 1:58:05 PM

sciencedaily.com

Researchers identify nerve-guiding protein that aids pancreatic cancer spreadDate:August 10, 2015Source:Johns Hopkins MedicineSummary:Scientists have identified a molecular partnership in pancreatic cancer cells that might help to explain how the disease spreads -- metastasizes -- in some cases. Their findings reveal urgently needed new targets to treat pancreatic cancer, which strikes nearly 50,000 people in the US each year and has only a 5 percent survival rate five years after diagnosis.Share:
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FULL STORY

Scientists at the Johns Hopkins Kimmel Cancer Center have identified a molecular partnership in pancreatic cancer cells that might help to explain how the disease spreads -- metastasizes -- in some cases. Their findings reveal urgently needed new targets to treat pancreatic cancer, which strikes nearly 50,000 people in the U.S. each year and has only a 5 percent survival rate five years after diagnosis.

One of the molecular partners is annexin A2, a protein that scientists say was already linked to poor survival rates in these cancers. In a report published in the Aug. 4 issue of Science Signaling, Lei Zheng, M.D., Ph.D., and his colleagues show that annexin A2 helps usher a protein called Sema3D out of pancreatic cancer cells. Once outside the cells, Sema3D joins with another molecule to fuel the cancer's spread. Sema3D is a protein that guides the projecting arms of nerve cells, called axons, as the nerve cells grow and develop.

In experiments with mice, the researchers calculated a seventyfold drop in the amount of Sema3D secreted from mouse pancreatic cancer cells in animals that lacked annexin A2. In an experiment involving 23 mice, none of the annexin-free animals developed visible metastatic tumors. By contrast, 16 out of 17 mice that produced annexin A2 in their cells developed metastatic tumors in the liver, lungs or abdominal cavity.

In a second group of experiments using human tissue from patients with pancreatic ductal adenocarcinoma, which accounts for more than 90 percent of pancreatic cancers, Zheng and his colleagues also tracked down a link between the abundance of Sema3D in those tissues and the progression of metastatic pancreatic cancer.

The team reports that Sema3D was abundant in the main tumor tissue of only three of 13 (23 percent) patients who died after minimal cancer spread. But it was abundant in the main tumors of 14 of 22 (64 percent) patients who died with widely metastatic cancer, and also in the metastatic tumors of 17 of 23 (74 percent) patients.

The presence of Sema3D also seems to be associated with the recurrence of pancreatic cancer in patients whose primary tumors were surgically removed, the scientists say. Sema3D was abundant in the primary tumors of 15 of 20 patients (75 percent) who lived free of the cancer for less than a year after their surgery, compared to only four of 15 (27 percent) patients who lived disease-free for more than two years after surgery.

With their new data in hand, the researchers are pursuing three possible therapeutic targets to stop pancreatic cancer metastasis driven by annexin A2 and Sema3D. "We are planning clinical trials with a recently developed vaccine to target annexin A2," says Zheng, an associate professor of oncology and surgery at the Johns Hopkins University School of Medicine. "But at the same time, we are also developing a therapeutic antibody targeting annexin A2, and we are looking for a small molecule that would inhibit Sema3D."

Zheng and colleagues emphasize they don't know precisely how the Sema3D encourages the spread of pancreatic cancer, but they think it may help cancer cells surround and track nerves to travel away from the main tumor.

This neural highway might be especially important in pancreatic cancer, they say, because it grows fewer blood vessels that can carry cancer cells to the rest of the body. "More so than some other cancers, pancreatic cancers are what we call neurotropic, meaning that they tend to invade nerves," explains Zheng.

It's also unclear at this point, he says, exactly how annexin A2 encourages pancreatic cancer cells to release Sema3D, but the researchers suspect annexin A2 may act like a bodyguard to Sema3D, sheltering and guiding the protein as it makes its way toward an exit at the cell surface. Or, they speculate, it may act more like a professional packer, helping to enclose Sema3D in tiny molecular bubbles called vesicles before it is secreted by the cell.

Zheng and his colleagues became interested in annexin A2's exact role in cancer spread after noting a curious effect in a trial of the pancreatic cancer vaccine GVAX, first developed by Johns Hopkins researchers.

In a 2011 vaccine trial of patients whose primary pancreatic tumors were surgically removed, "we found antibodies against annexin A2 in those who had received the vaccine and who also had demonstrated long-term, disease-free survival after receiving the vaccines," explains Zheng. "This suggested to us that we should study annexin's role in pancreatic cancer progression."

Story Source:

The above post is reprinted from materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.

Journal Reference:

K. Foley, A. A. Rucki, Q. Xiao, D. Zhou, A. Leubner, G. Mo, J. Kleponis, A. A. Wu, R. Sharma, Q. Jiang, R. A. Anders, C. A. Iacobuzio-Donahue, K. A. Hajjar, A. Maitra, E. M. Jaffee, L. Zheng. Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer. Science Signaling, 2015; 8 (388): ra77 DOI: 10.1126/scisignal.aaa5823

[IRWIN JAMES FRANKEL] Stanford does it: sciencemag.org SYNTHETIC BIOLOGY Modified yeast produce opia...

IRWIN JAMES FRANKEL — 8/16/2015 3:30:28 PM

Stanford does it:

sciencemag.org

SYNTHETIC BIOLOGY
Modified yeast produce opiates from sugar
Robert F. Service

Related Resources
In Science Magazine
REPORT Complete biosynthesis of opioids in yeastStephanie Galanie et al.Science aac9373Published online 13 August 2015

Move over, poppies. In one of the most elaborate feats of synthetic bio logy to date, a research team has engineered yeast with a medley of plant, bacterial, and rodent genes to turn sugar into thebaine, the key opiate precursor to morphine and other powerful painkilling drugs that have been harvested for thousands of years from poppy plants. The team also showed that with further tweaks, the yeast could make hydrocodone, a widely used painkiller that is now made chemically from thebaine.

“This is a major milestone,” says Jens Nielsen, a synthetic biologist at Chalmers University of Technology in Göteborg, Sweden. The work, he adds, demonstrates synthetic biology's increasing sophistication at transferring complex metabolic pathways into microbes.

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ILLUSTRATION: A. CUADRA/SCIENCE

By tweaking the yeast pathways, medicinal chemists may be able to produce more effective, less addictive versions of opiate painkillers. But some biopolicy experts worry that morphinemaking yeast strains could also allow illicit drugmakers to brew heroin as easily as beer enthusiasts home brew today—the drug is a simple chemical conversion from morphine. That concern is one reason the research team, led by Christina Smolke, a synthetic biologist at Stanford University in Palo Alto, California, stopped short of making a yeast strain with the complete morphine pathway; medicinal drug makers also primarily use thebaine to make new compounds.

Synthetic biologists had previously engineered yeast to produce artemisinin, an antimalarial compound, but that required inserting just a handful of plant genes. To get yeast to make thebaine, Smolke's team coaxed the cells to express 21 genes in total, including many added from a diverse set of species (see graphic); making hydrocodone took 23 genes.

Their success, reported online this week in Science, caps a race to install the complex opioid pathway in yeast. Last year, Smolke's team reported engineering yeast to carry out the tail end of the process, going from thebaine to morphine. In April, Vincent Martin, a microbiologist at Concordia University in Montreal, Canada, and his colleagues said they had created yeast that could go from an earlier intermediate compound called R-reticuline to morphine. A few weeks later, John Dueber, a synthetic biologist at the University of California, Berkeley, and colleagues announced yeast that carries out most of the first half of the pathway, going from glucose to another intermediate compound, S-reticuline. Finally, two groups reported in late June that they had identified the long-sought enzyme needed to carry out the chemical transformation in the middle, S-reticuline to R-reticuline.

Even so, many predicted it would take years to put all the pieces together. As it turns out, back in May, Smolke and her colleagues had already largely finished the task. “It shows this field is really moving fast,” says Kenneth Oye, a biotechnology policy expert at the Massachusetts Institute of Technology in Cambridge.

The most important challenge, Smolke says, was increasing the efficiency of each step so losses wouldn't build up. In one step, for example, a plant enzyme called SalSyn was doing a poor job of converting R-reticuline to another compound called salutaridine. Eventually, Smolke's team discovered that the yeast made the enzyme incorrectly, attaching the wrong sugars to it. The researchers fixed the problem by reengineering the inserted plant gene.

Smolke plans to go on tinkering. The microbes need to increase output of thebaine by a factor of 100,000 for drug companies to be interested in using them to make medicines. That won't be easy. But Martin notes that researchers boosted the output of the artemisininmaking yeast by a similar amount. “It will happen,” he says. “The only question is how fast.” Smolke recently formed a company called Antheia, based in Palo Alto, that aims to push that pace.

To keep up with the yeast engineers, Oye says policy experts need to develop rules to limit the risk of unintended uses of engineered microbes. In the case of opiatemaking yeast, such rules might forbid developing strains to produce illicit drugs, such as heroin, and require scientists to build in genes that prevent the microbes from living outside of a controlled laboratory environment.

Not everyone is worried about home-brewed opiates. Andrew Ellington, a synthetic biologist at the University of Texas, Austin, calls such fears “overblown.” The idea that producing vanishingly small quantities of opiates through fermentation is somehow going dwarf the problem of illegal drugs made from poppies is “laughable,” he says. But Martin disagrees. “Poppy fields are not readily available to someone in Chicago, whereas yeast can be made available to anyone.”

The editors suggest the following Related Resources on Science sitesIn Science Magazine

[tom pope] Getting complicated. reuters.com

tom pope — 3/17/2015 10:16:14 PM