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Targeting cancer stem cells improves treatment effectiveness, prevents metastasis Science Daily ... Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma the most common head and neck cancer and the second-most common skin cancer, according to a new study. Ascorbic Acid: New Potential In Targeting Cancer Stem CellsScience Times all 16 news articles »

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Skin Stem Cells Comments Off on Targeting cancer stem cells improves treatment effectiveness, prevents metastasis – Science Daily | March 11th, 2017

March 09, 2017 07:03 ET | Source: Neuralstem, Inc.

-NSI-566 Achieved Robust Engraftment and Long-Term Survival After Transplantation-

- Data Published in Journal of Neurotrauma-

GERMANTOWN, Md., March 09, 2017 (GLOBE NEWSWIRE) -- Neuralstem, Inc. (Nasdaq:CUR), a biopharmaceutical company focused on the development of nervous system therapies based on its neural stem cell technology, announced the recent publication of preclinical data on NSI-566 spinal cord-derived neural stem cells in Journal of Neurotrauma. These data showed robust engraftment and long-term survival of NSI-566 post transplantation in a rat model of penetrating ballistic-like brain injury (PBBI). NSI-566 is Neuralstems lead stem cell therapy candidate.

The study entitled, Amelioration of penetrating ballistic-like brain injury induced cognitive deficits after neuronal differentiation of transplanted human neural stem cells," was led by Ross Bullock, M.D., Ph.D., The Miami Project to Cure Paralysis, University of Miami School of Medicine. These are the first data from the 4-year proof-of-concept research program, funded by the United States Department of Defense, for NSI-566 in traumatic brain injury.

These data on NSI-566 are encouraging, particularly since researchers have long been challenged to achieve durable engraftment and survival of neural stem cells after transplantation, said Dr. Bullock. No long-term treatment beyond physical therapy is currently available to restore cognition after a traumatic brain injury. Transplantation of stem cells into the injured brain may allow a unique replacement therapy and fill a significant medical need.

Researchers transplanted NSI-566 into rats 7-10 days after PBBI. The rats were immunosuppressed to enable survival of NSI-566 neural stem cells. Robust engraftment with evidence of prominent neuronal differentiation was observed after 4 months, and axons from grafted cells extended a significant distance from the graft site along host white matter tracts.

These data continue to support our research and development platform. The results provide additional insight into our proprietary regionally specific stem cells and their potential benefits in nervous system disorders, said Karl Johe, Ph.D., Chief Scientific Officer, Neuralstem. We look forward to additional preclinical data from this collaboration with Dr. Bullocks group to support the potential use of NSI-566 in traumatic brain injury.

About Neuralstem Neuralstems patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system diseases and conditions.

Neuralstems technology enables the discovery of small molecule compounds by systematic screening chemical compounds against its proprietary human hippocampal stem cell line. The screening process has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brains capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central nervous system (CNS) conditions.

The company has completed Phase 1a and 1b trials evaluating NSI-189, a novel neurogenic small molecule product candidate, for the treatment of major depressive disorder or MDD, and is currently conducting a Phase 2 efficacy study for MDD.

Neuralstems stem cell therapy product candidate, NSI-566, is a spinal cord-derived neural stem cell line. Neuralstem is currently evaluating NSI-566 in three indications: stroke, chronic spinal cord injury (cSCI), and Amyotrophic Lateral Sclerosis (ALS).

Neuralstem is conducting a Phase 1 safety study for the treatment of paralysis from chronic motor stroke at the BaYi Brain Hospital in Beijing, China. In addition, NSI-566 was evaluated in a Phase 1 safety study to treat paralysis due to chronic spinal cord injury as well as a Phase 1 and Phase 2a risk escalation, safety trials for ALS. Subjects from all three indications are currently in long-term observational follow-up periods to continue to monitor safety and possible therapeutic benefits.

Cautionary Statement Regarding Forward Looking Information This news release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by words such as expect, anticipate, intend, plan, believe, seek or will. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to differ materially from those expressed in our forward-looking statements include risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstems periodic reports, including the Annual Report on Form 10-K for the year ended December 31, 2015, and Form 10-Q for the nine months ended September 30, 2016, filed with the Securities and Exchange Commission (SEC), and in other reports filed with the SEC. We do not assume any obligation to update any forward-looking statements.

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Neuralstem Announces Publication of NSI-566 Data in a Rodent Model of Traumatic Brain Injury - GlobeNewswire (press release)

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The following are some of the biotech stocks that made their way onto the Day's Gainers & Losers' list of March 9, 2017.

GAINERS

1. Ocera Therapeutics Inc. (OCRX)

Gained 71.82% to close Thursday's trading at $1.89.

News: The Company reported additional encouraging results from its Phase 2b STOP-HE study of intravenous (IV) OCR-002 in hospitalized patients with Hepatic Encephalopathy.

The initial STOP-HE results, reported in January 2017, had demonstrated highly statistically significant reduction in ammonia levels over placebo, strong evidence of benefit across multiple endpoints with higher doses (15g, 20g), clinical improvement dose trend, increased responder rate with increased dose and superiority over placebo at all doses. OCR-002 was also safe and well-tolerated.

The additional study data revealed on Thursday indicates that IV OCR-002 provided clinical benefit over placebo in other parameters as well, such as the Physician Overall Evaluation, Model for End-Stage Liver Disease (MELD) scores, and in renal function as measured by the change from baseline in Blood Urea Nitrogen (BUN) levels.

2. Cymabay Therapeutics Inc. (CBAY)

Gained 20.29% to close Thursday's trading at $4.09.

News: The Company will provide a corporate overview at the 29th Annual ROTH Conference on March 13th and at the Oppenheimer 27th Annual Healthcare Conference on March 21st.

Near-term catalysts:

- The results from phase II study of Cymabay's investigational drug Seladelpar in primary biliary cholangitis are expected in 3Q 2017. - The company's most advanced product candidate is Arhalofenate for treatment of gout, which has completed phase II studies. The drug candidate is licensed to Kowa Pharmaceuticals America, Inc. in the U.S.

Licensing discussions for other territories are underway. Ex-US licensing agreement for Arhalofenate is expected to be inked this year.

3. Neuralstem Inc. (CUR)

Gained 19.64% to close Thursday's trading at $5.30.

News: The preclinical data of the Company's NSI-566 spinal cord-derived neural stem cells in a rodent model of traumatic brain injury shows robust engraftment and long-term survival. The data are published in Journal of Neurotrauma.

NSI-566 is being explored in three indications: stroke, chronic spinal cord injury (cSCI), and Amyotrophic Lateral Sclerosis (ALS).

A phase I safety study of NSI-566 for the treatment of paralysis from chronic motor stroke is being conducted at the BaYi Brain Hospital in Beijing, China. In addition, NSI-566 was evaluated in a Phase 1 safety study to treat paralysis due to chronic spinal cord injury as well as a Phase 1 and Phase 2a risk escalation, safety trials for ALS. Subjects from all three indications are currently in long-term observational follow-up periods to continue to monitor safety and possible therapeutic benefits, according to the company.

Near-term catalyst:

-- Data from a phase II trial of NSI-189 for the treatment of major depressive disorder is expected in 3Q 2017.

4. Immunomedics Inc. (IMMU)

Gained 19.48% to close Thursday's trading at $6.01.

News: A global licensing agreement between Seattle Genetics (SGEN) and Immunomedics, worth over $2 billion, has been put on hold by a Delaware judge, following an injunction filed by venBio Select Advisor LLC, the largest shareholder of Immunomedics, to block the deal.

The license agreement between Seattle Genetics and Immunomedics was signed last month, and it involves antibody-drug conjugate, Sacituzumab govitecan, or IMMU-132.

Sacituzumab Govitecan (IMMU-132) is Immunomedics' lead investigational drug. As part of the agreement, Seattle Genetics is responsible for initiating phase III clinical trials of IMMU-132 in patients with metastatic triple-negative breast cancer (TNBC) and will be responsible for submitting the initial Biologics License Application to the FDA for accelerated approval.

VenBio is seeking to thwart the deal saying it undervalues the potential of IMMU-132. Now that a temporary restraining order has been placed on the deal, maybe there is an opportunity for a better deal.

5. Curis Inc. (CRIS)

Gained 20.78% to close Thursday's trading at $3.08.

News: The Company reported Q4 and full-year 2016 financial results and updated the progress of its pipeline.

The net loss for Q4, 2016 narrowed to $11.3 million or $0.08 per share on total revenue of $2.36 million. This compared with a net loss of $13.5 million or $0.10 per share and total revenue of $2.09 million in the year-ago period.

As for its clinical pipeline, the company noted that its phase I trial for CA-170 continues to progress on track through the dose escalation stage, and extension of the CA-170 Phase 1 study is all set to begin with enrollment of immunotherapy-nave patients in Korea and Spain, and with additional trial centers in other European countries projected to open in the second quarter.

A phase II trial of another drug candidate CUDC-907 in patients with relapsed/refractory MYC-altered diffuse large B cell lymphoma, or DLBCL , is expected to complete enrollment within the first half of this year.

6. VIVUS Inc. (VVUS)

Gained 16.35% to close Thursday's trading at $1.21.

News: The Company reported Q4 and full-year 2016 financial results.

VIVUS reversed to profit in the fourth quarter and full year of 2016 from net losses in the comparable year-ago periods.

Net income for the 2016 fourth quarter and full year was $56.6 million or $0.54 per share and $23.3 million or $0.22 per share, respectively, as compared to a net loss of $12.2 million or $0.12 per share and $93.1 million or $0.90 per share in 2015, respectively.

VIVUS had cash, cash equivalents and available-for-sale securities of $269.5 million at December 31, 2016.

The company noted that it will use its strong cash position for the acquisition and development of a new product pipeline to drive value creation for its stockholders while addressing the unmet needs of patients.

7. TG Therapeutics Inc. (TGTX)

Gained 16.26% to close Thursday's trading at $11.80. Shares of TG Therapeutics have been on the rise since announcing positive top line data from its phase III trial of TG-1101 in patients with high risk Chronic Lymphocytic Leukemia, dubbed GENUINE, on March 6, 2017.

News: The Company has priced an underwritten public offering of 5,128,206 shares of its common stock at a price of $9.75 per share.

Anticipated event: Q4 and full-year 2016 financial results and an update on business outlook for 2017 are slated to be presented on March 10, 2017.

LOSERS

1. InspireMD Inc. (NSPR)

Lost 37.56% to close Thursday's trading at $1.23.

News: The Company has priced its public offering of shares of Series C Convertible Preferred Stock, Series B warrants and Series C warrants.

Each share of Series C Convertible Preferred Stock is convertible into 4 shares of common stock at a conversion price equal to $1.60 per share. The Series B warrants have an exercise price of $2.00 per share of common stock and Series C warrants have an exercise price of $1.60 per share of common stock.

The gross proceeds from the offering are estimated to be up to $7.5 million. The offering is expected to close on or about March 14, 2017.

2. Cogentix Medical Inc. (CGNT)

Lost 13.12% to close Thursday's trading at $1.92.

News: The Company reported Q4 and full-year 2016 financial results.

Net loss for Q4 2016 widened to $18.57 million or $0.40 per share on revenue of $13.2 million. This compared with a net loss of $1.09 million or $0.04 per share and revenue of $13.64 million in the year-ago period.

3. BIOLASE Inc. (BIOL)

Lost 12.41% to close Thursday's trading at $1.20.

News: The Company reported Q4 and full-year 2016 financial results

The net loss for the fourth quarter of 2016 widened to $4.4 million or $0.07 per share as revenues declined to $13.8 million. This compared with a net loss of $2.5 million or $0.04 per share and revenue of $14.5 million in the fourth quarter of 2015.

4. Tandem Diabetes Care Inc. (TNDM)

Lost 11.63% to close Thursday's trading at $1.90.

News: The Company reported Q4 and full-year 2016 financial results.

The net loss for the fourth quarter of 2016 widened to $14.82 million or $0.48 per share as sales fell to $28.91 million. This compared with a net loss of $12.09 million or $0.40 per share and sales of $29.12 million in the fourth quarter of 2015. Tandem has also filed a registration statement on Form S-1 with the SEC relating to a proposed follow-on public offering of approximately $50 million of its common stock.

by RTT Staff Writer

For comments and feedback: editorial@rttnews.com

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Gainers & Losers Of Mar.9: CBAY, IMMU, TGTX, NSPR, TNDM... - RTT News

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TiGenix Announces Positive Topline Week-104 Data for Cx601 ADMIRE-CD Trial P&T Community Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product candidate, AlloCSC-01, is currently in a Phase II clinical trial in Acute Myocardial Infarction (AMI). In addition, the second product candidate from the cardiac stem ... and more »

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Numerous people may say they want to grow up to be a heart surgeon, but very few actually achieve that goal. Holly Mewhort, MD, PhD, is one who has done so. And thats not the only thing Mewhort, who is part of the Libin Cardiovascular Institute of Albertas cardiac surgical residency program, has accomplished.

She has also excelled in basic and translational research. She recently received international recognition for her work in cardiac research, winning the Vivien Thomas Young Investigator Award from the American Heart Association, a prestige award given to early investigators who are focusing on fundamental and applied surgical research.

That research was done as part of her PhD program, which she completed in June 2016 under the supervision of Libin Institutes Paul Fedak, MD, PhD. Fedak is a cardiac surgeon and basic/translational researcher who directs the Marlene and Don Campbell Family Cardiac Research Laboratory at the Cumming School of Medicine.

Research shows biomaterial can trigger healing in damaged heart muscle

Mewhorts research investigates the use of biomaterial in regenerating and restoring heart tissue in patients who had previously suffered a heart attack. The material, CorMatrix-ECM, is a connective tissue matrix surgically applied to damaged heart tissue to trigger healing.Mewhort describes the material as providing the scaffolding that holds cells together and influences their behaviour and survival.

Her research in this area began four years ago in the lab and has had great success. In preclinical trials, the project has shown that this bio-material can restore function to damaged heart muscle by promoting the formation of new blood vessel networks a process called vasculogenesis.

The investigators have completed a pilot clinical trial, which saw the patch applied to the heart tissue of a handful of patients during coronary bypass surgery. The results havent been published yet, but the data looks promising.

Mewhort is thrilled to be part of a research project that has been successfully translated from bench to bedside. If it works at the clinical trial level, this could be a game-changer for patients who have suffered a heart attack, she says, noting until now, there hasnt been a way of restoring function to damaged heart tissue in those patients.

Cardiac surgery research program is 'cutting edge'

Its also exciting for Mewhort to win the same award her mentor, Dr. Paul Fedak, received 14 years ago. He was also a cardiac surgery trainee pursuing a PhD, investigating stem cell regeneration of heart tissue. The fact that two researchers connected with the University of Calgary earned the same international award is impressive, as competition is stiff. Past winners have studied at such institutions as the University of Toronto, Duke and Stanford.

Fedak, who studied at the University of Toronto, was recruited to come to Calgary about a decade ago and has since set up a cutting-edge cardiac surgery research program. Mewhort is the first PhD graduate of his laboratory. As her mentor, Fedak, who, besides being an academic researcher is a full-time clinical heart surgeon, is pleased to see the program turning out well-respected young academic surgical scientists.

He says Mewhorts award fulfils another career goal, explaining that when he won the Vivien Thomas Young Investigator Award his desire became to see one of his students do the same. For Fedak, the award signifies the coming-of-age of academic cardiac surgeon training in Calgary.

This shows us how far we have come with our program, he says.

Receiving her mentors praise is a big deal for Mewhort, as Fedak was one of the reasons she chose to pursue her surgery training and PhD in Calgary. Mewhorts future looks bright as she continues her residency in cardiac surgery on campus with the ultimate goal of having an active surgical and research career, much like her mentor.

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JaCeon Golden has only ever known the inside of hospitals. But the treatment hes receiving may have implications far beyond his as-yet isolated life.

Round-faced and big-eyed, with a perpetual pout that belies his sunny nature, he looks as healthy as any other 5-month-old. But JaCeon was born without a functioning immune system. Even the most banal of infections a cold, a diaper rash could be deadly.

Earlier this year, JaCeon became the first baby at UCSF Benioff Childrens Hospital at Mission Bay to undergo an experimental gene therapy treatment that, doctors hope, will nudge his body to build a new, robust immune system.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who is being held by patient care assistant Grace Deng at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Hawkins brought her nephew Golden from New Mexico for the experimental treatment.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who...

So far, his results are promising. In a few weeks, JaCeons great aunt, whos also his guardian, hopes to introduce him to the world outside.

Am I going to see him smile when we walk out of here? Dannie Hawkins, 52, said with a glance at the baby, being fed from a bottle by a nurse wearing a gown and gloves. Hows he going to do in the free world?

It will be a while months, probably years before JaCeon is able to fully integrate with that wide world: go to school and birthday parties, ride a public bus, swim in a community pool. But that those activities may be in his future at all is extraordinary.

The treatment given to JaCeon is the result of decades of research into gene therapy that included a string of striking failures that led many doctors to abandon the pursuit altogether.

Gene therapy long had been considered a potential treatment for severe combined immunodeficiency disorder, or SCID, the condition JaCeon was born with, and some other genetic syndromes. The idea is to replace a single gene thats causing trouble.

Even as many doctors gave up on the promise of gene therapy, teams of stubborn scientists kept plugging away. And a few years ago, their experiments started to work, propelled by advances in the understanding of stem cells in this case, a type called hematopoietic stem cells that live in bone marrow and are responsible for generating blood and immune cells and improved methods of delivering genetic repairs.

JaCeon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski.

JaCeon Golden is treated by patient care assistant Grace Deng...

Now human gene therapy is being tested in trials at UCLA, where a team has treated 20 children with one type of SCID, and at UCSF in collaboration with St. Jude Childrens Research Hospital in Memphis. Both trials are funded by grants from the California Institute for Regenerative Medicine, the states stem cell agency, located in Oakland.

Researchers are studying similar therapies in hopes of curing genetic syndromes like sickle cell disease. And the stem cell agency is funding gene therapy research into potential treatments for HIV, brain cancer and Huntingtons disease, among others.

Gene therapy has been shown to work, the efficacy has been shown. And its safe, said Sohel Talib, a senior science officer at the state stem cell agency. The confidence has come. Now we have to follow it up.

JaCeon was born at a hospital in Las Cruces, N.M., and diagnosed with SCID just after birth as part of a standard newborn screening. He was flown to UCSF, one of a handful of facilities with expertise in SCID, when he was 3 weeks old. His great-aunt joined him about a month later, in November.

The immune disorder is commonly known as bubble baby disease, because until fairly recently kids born with it had to live in isolation, often in plastic bubbles in hospital rooms or their own homes to protect them from infections.

Babies born with SCID have a genetic mutation that leaves their immune system unable to develop disease-fighting cells. Without treatment, most will die within a year. Since the 1970s, some babies with SCID were cured with a bone-marrow transplant. But to be effective, a perfect match was required, almost always from a sibling, and only about a fifth of kids have such a match.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as Deng bottle feeds Golden at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Golden was brought from New Mexico for the experimental treatment.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as...

The rest could undergo a bone marrow transplant from a partial match in JaCeons case, his great-aunt was one but even when that treatment was successful, kids were left with fragile immune systems that required constant maintenance with antibiotics and other boosts.

Gene therapy, though, may prove as effective as a bone marrow transplant from a perfect match.

The procedure starts with doctors harvesting stem cells from a babys own bone marrow, usually taken from the hip. In JaCeons case, his stem cells were sent in January to St. Jude in Memphis, where scientists are perfecting the gene-therapy delivery mechanism.

Sending away JaCeons stem cells was probably the most stressful time of my life, short of my own kids maybe being born, said Dr. Morton Cowan, the lead investigator of the UCSF trial, who has worked in SCID research for more than 30 years.

JaCeons stem cells were flown east over the first big weekend of major storms in California. Flights were being canceled around the clock, and doctors only had a window of about 36 hours to get the fresh cells to the labs in Memphis.

The trip was successful, but not without a hitch. After the cells were engineered and were being sent back to California, the material for a few heart-stopping hours got lost in the mail.

In a couple of months, Cowan said, he hopes to be able to do the gene-therapy delivery at UCSF labs, avoiding the travel headaches.

For now, that still happens at St. Jude. Doctors used a virus in fact, HIV, the virus that causes AIDS to deliver the gene therapy to JaCeons stem cells. The virus is neutered, with all of the disease-causing pieces inside removed.

Whats left is a missile-like shell designed to infiltrate a cell and deliver whatever payload doctors have inserted inside in this case, a healthy gene that will restore the stem cells ability to build normal immune cells.

Back in San Francisco, the cells were infused into JaCeon via a port in his chest. Because theyre his own cells, there was no fear his body would reject them.

He did have to undergo mild chemotherapy to kill off some of his own bone marrow and make room for the re-engineered stem cells to roost, but UCSF has been developing a technique for limiting the dosage of chemotherapy given in gene therapy procedures.

JaCeon suffered no obvious side effects from either the stem cell infusion or the chemotherapy drugs, doctors said.

Hes just thriving. Hes just hes great, Cowan said. He added, We cant open the Champagne just yet, but early tests show the new gene is active, and JaCeon has had an uptick of certain immune cells.

The infusion procedure took just 20 minutes, and JaCeon slept through it, but it felt momentous nonetheless.

It had been difficult to decide to enroll JaCeon in the trial, Hawkins said. Since she was a partial match for a bone marrow transplant, she had the option of giving him the traditional and well-tested therapy.

Shed said to his doctors, So youre telling me hes a guinea pig? They told her, she recalls, If it works, he can open the door for other kids.

That night, as Hawkins slept on the decision, I kept waking up, waking up, all night long, she said. If there was a possibility he could save someone else ... she added, and then broke off in tears.

She spends about six hours with JaCeon every day, beginning each morning with a bath in sterile water, brought by nurses in special tubs. Shes constantly wiping down his toys, clothes, bedding and stuffed animals.

Ive changed a lot of diapers in my time, but this is way more complicated than with other kids, Hawkins said, demonstrating the multistep process she uses to prevent diaper rash.

Im not going to say its been easy, she said. But hes doing fine. I wouldnt have it any other way.

Erin Allday is a San Francisco Chronicle staff writer. Email: eallday@sfchronicle.com

Twitter: @erinallday

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By studying the cannabilistic tendency of cancer cells, my research team has made some progress in finding out why.

The chances of recurrence and disease outcome vary with cancer subtype. About one-third of patients diagnosed with triple negative breast cancer, the most aggressive subtype, may experience a recurrence in another part of the body. This is called distant recurrence.

It has been difficult, if not impossible, to predict if and when the same cancer will recur and to stop it. Recurrent disease may arise from just a single cancer cell that survived the initial treatment and became dormant. The dormancy allowed it to hide somewhere in the body, not growing or causing harm for an unpredictable amount of time.

Determining what puts these dormant cells to sleep and what provokes them to wake up and begin multiplying uncontrollably could lead to important new treatments to prevent a demoralizing secondary cancer diagnosis.

Recently, my research team and I uncovered several clues that might explain what triggers these breast cancer cells to go dormant and then reawaken. We showed that cell cannibalism is linked to dormancy.

How do bone stem cells affect breast cancer?

Breast cancer can recur in the breast or in other organs, such as the lungs and bone. Where breast cancer decides to grow depends largely on the microenvironment. This refers to the cells that surround it, including immune cells, cells comprising blood vessels, fibroblasts and the select proteins they produce, among other factors.

Over a century ago, a surgeon named Stephen Paget famously compared the organ-specific prevalence of cancer metastasis to seeds and soil. Because breast cancer often relapses in bones, in this metaphor, which still holds forth today, the bone marrow provides a favorable microenvironment (the soil) for dormant breast cancer cells (the seeds) to thrive.

Just as seeds need soil to provide an environment for growth, cancer cells need an environment to grow. From http://www.shutterstock.com

Thus, a substantial amount of recent work has involved trying to determine the role in cancer dormancy of a special type of cell, called mesenchymal stem cells (MSCs). These are found in bone marrow.

MSCs in bone marrow are highly versatile. They are able to form bone, cartilage and fibrous tissue, as well as cells that support the immune system and formation of blood. They are also known to travel to sites of tissue injury and inflammation, where they aid in healing.

Breast cancer cells readily interact with MSCs if they meet in the bone marrow. They also readily interact if the breast cancer cells recruit them to the site of the primary tumor.

My research team and I recently focused on potential outcomes of these cellular interactions. We found an odd thing happens, which may provide insight into how these breast cancer cells hide for a long time.

In the laboratory setting, we produced breast tumor models containing MSCs. We also re-created the hostile conditions that naturally challenge developing tumors in patients, such as localized nutrient deficits caused by rapid growth of cancer cells and overcrowding.

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How 'Cannibalism' By Breast Cancer Cells Promotes Dormancy: A Possible Clue Into Cancer Recurrence - IFLScience

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An adult stem cell center established by the Kansas Legislature in 2013 is almost ready for its first clinical trial.

Buddhadeb Dawn, executive director of the Midwest Stem Cell Therapy Center, told legislators Tuesday that the trial will focus on treating graft-versus-host disease and will begin after final approvals from the U.S. Food and Drug Administration.

Our goal was to do this (trial) in January, but we got delayed because of different things, Dawn said during a hearing of the House Health and Human Services Committee. So we are now hoping to start it perhaps in summer.

Based at the University of Kansas Medical Center in Kansas City, the stem cell center has analyzed trials done elsewhere and hosted a clinical trial sponsored by a biotech company that uses modified stem cells from bone marrow to treat stroke.

But the graft-versus-host disease trial would be the first homegrown one.

Graft-versus-host disease is a potential complication when a patient receives a transplant of tissue, like an organ or bone marrow, from another person.

The disease occurs when transplanted tissue fights the patients natural immune system, potentially damaging the liver, skin or other areas. Its a rare illness, with about 20,000 cases in the United States each year.

Rep. Randy Powell, a Republican from Olathe, said the trial was a welcome and exciting development. He said his wife is at risk for the illness following treatment for leukemia.

I know that graft-versus-host is a big thing, Powell said. I think my wife still has an annual checkup where they keep their eye out (to make sure) thats not sticking its head up and causing issues.

Dawn said the center would like to take the next step and move into clinical trials using adult stem cells to treat things like joint ailments, diabetes and amyotrophic lateral sclerosis, also known as Lou Gehrigs disease.

But the regulatory process takes time.

Wed like to be able to offer a portfolio of different disease conditions that adult stem cells can benefit, Dawn said. Im hoping that within the next five years we would at least have some FDA approval for treatment with adult stem cells for other conditions.

Dawn said successful trials could lead to more private investment dollars so we are self-sustaining at some point in the future.

The centers reliance on state funds has been a point of contention for fiscally conservative legislators in the past. Most of the facilitys budget still comes from the states payment, which was reduced by about $28,000 to $754,500 last year.

Thats far less than what stem cell research facilities in other states receive.

Doug Girod, executive vice president of the KU medical center, said that given the budget, Dawn and his small team have done remarkable work.

We could be 10 times bigger than we are and doing 10 times as much if we had the resources, Girod said. But I think were maximizing every opportunity we can with what we have right now.

The center was spearheaded by socially conservative legislators, including Sen. Mary Pilcher-Cook, to showcase adult stem cell research as an alternative to using stem cells derived from human embryos.

About $56,000 of its annual budget goes to educating the public about the differences between embryonic stem cells and adult cells and hosting an annual conference about advances in adult stem cell treatment.

Rep. John Wilson, a Democrat from Lawrence, said he initially was skeptical about the facility because he thought the Legislature was inserting itself into a religious or philosophical fight. But he said his attitude has changed.

Im glad that despite my opposition to it the state has gone forward with funding some really terrific research, Wilson said. My concern now is how do we take it to the next level so all of this hasnt been for nothing.

Andy Marso is a reporter for KMUW's Kansas News Service, a collaboration of KMUW, Kansas Public Radio and KCUR covering health, education and politics in Kansas. You can reach him on Twitter@andymarso.

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Atlanta Falcons linebacker Paul Worrilow kisses his 15-month-old daughter, Julie, after the first day of training camp in Flowery Branch, Ga., on July 28, 2016.(Photo: Curtis Compton, Associated Press)

Height, weight: 6 feet, 230 pounds.

Joined the Lions:Worrilow, who turns 27 in May, agreed to a one-year contract with the Lions on Wednesday.

NFL career: He made the Atlanta Falcons in 2013 as an undrafted free agent after being a walk-on at Delaware. Worrilow was the Falcons' starting middle linebacker job in 2013-15. He led the team in tackles each of his first two seasons. Last season, the Falcons wanted to get faster at linebacker, so they drafted two, and Worrilow lost his job to rookie Deion Jones. Worrilow was relegated mostly tospecial teams in 2016 and played just four defensive snaps in the playoffs -- none in the Super Bowl.I know I can go and play good ball, Worrilow told the Atlanta Journal-Constitution. Whether if thats here or somewhere else.

Off the field:In 2011, he signed up for Delawares bone-marrow program. He underwent a six-hour procedure to donate peripheral blood stem cells to an anonymous 21-year-old leukemia patient.

Lions to make Ricky Wagner highest-paid RT; he's 'living his dream'

Contact Carlos Monarrez: cmonarrez@freepress.com. Follow him on Twitter @cmonarrez.

Download our free Lions Xtra app on your Apple and Android devices.

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Lions LB Paul Worrilow gave stem cells to anonymous leukemia patient - Detroit Free Press

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Cedars-Sinai investigators have identified a stem cell-regulating gene that affects tumor growth in patients with brain cancer and can strongly influence survival rates of patients. The findings, published in the online edition of Scientific Reports, could move physicians closer to their goal of better predicting the prognosis of patients with brain tumors and developing more personalized treatments for them.

To enhance understanding of how glioma cancer stem cells (GCSCs) reproduce and how they affect patient survival, investigators spent three years analyzing the genetic makeup of more than 4,000 brain tumors. During their investigation, they identified the gene, called ZEB1, that regulates tumor growth. The investigators' analysis suggests that brain cancer patients who don't have the gene tend to have lower survival rates.

"Patients without the gene in their tumors have more aggressive cancers that act like stem cells by developing into an uncontrollable number of cell types," said John Yu, MD, vice chair of neurosurgical oncology in the Department of Neurosurgery and senior author of the study. "This new information could help us to measure the mutation in these patients so that we are able to provide a more accurate prognosis and treatment plan."

Brain cancer occurs when cancer cells -- also called malignant cells -- arise in the brain tissue. This year, more than 23,000 people will develop primary cancerous tumors of the brain. Approximately 16,000 of those patients will die, according to the National Cancer Institute and the American Cancer Society.

Yu and fellow researchers noted that while some brain cancer patients are born without the gene, others have it but over time, the gene has become less powerful -- which could have had a role in causing the disease.

"We found an 8 -month shorter survival rate in lower grade glioma patients with the ZEB1 gene mutation compared to those individuals who have the gene," said Yu, who also serves as director of Surgical Neuro-Oncology at Cedars-Sinai. "We are learning that some chemotherapies are not effective in the population of individuals who have the gene deletion so we have to treat them with different medications."

The study was funded by FasterCures, a center of the Milken Institute, and the National Institutes of Health, grant #NS048959.

Cedars-Sinai investigators who collaborated on the study included Keith L. Black, MD; Lincoln A. Edwards, PhD; Dror Berel; Mecca Madany; Nam-Ho Kim, PhD; Minzhi Liu; Mitch Hymowitz; Benjamin Uy; Rachel Jung; Minlin Xu; Altan Rentsendorj, PhD; and Xuemo Fan, MD, PhD.

Also contributing were researchers from Neuro-Oncology Branch, National Cancer Institute.

The Yu Laboratory focuses on immune and stem cell therapy for brain tumors, cancer stem cells and their microenvironment in brain tumors. Led by Yu, investigators have developed vaccine-based immunotherapy for brain tumors that led to multi-institutional, randomized placebo-controlled clinical trials, as well as bone marrow-derived neural stem cells for the treatment of cancer and neurodegenerative diseases.

Yu said future studies will explore specific drug regimens and their efficacy in patients with gene mutations of the stem cell gene.

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Materials provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.

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Neuroscientists pinpoint key gene controlling tumor growth in brain cancers - Science Daily

Bone Marrow Stem Cells Comments Off on Neuroscientists pinpoint key gene controlling tumor growth in brain cancers – Science Daily | March 10th, 2017

Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma the most common head and neck cancer and the second-most common skin cancer, according to a new study by cancer researchers at the UCLA School of Dentistry.

Head and neck squamous cell carcinoma is a highly invasive form of cancer and frequently spreads to the cervical lymph nodes. Currently, cisplatin is the standard therapeutic drug used for people with HNSCC. Yet, more than 50 percent of people who take cisplatin demonstrate resistance to the drug, and they experience a recurrence of the cancer. The five-year survival rates remain sorely low and researchers still dont understand the underlying mechanisms behind head and neck squamous carcinoma. Therefore, said UCLA cancer biologist Dr. Cun-Yu Wang, who led the study, theres an urgent need to understand why people with this type of cancer are resistant to therapy and to develop new approaches for treating it.

Wangs researchis published online today in the peer-reviewed journal Cell Stem Cell.

Cancer stem cells are known to be responsible for tumor formation and development; they also self-renew and tend to be unresponsive to cancer therapy. These cells have been found in head and neck squamous cell carcinoma. Given the unique challenges that cancer stem cells pose for oncologists, it remains unclear what the optimal therapeutic strategy is for treating HNSCC.

To address this, Wang, who holds the Dr. No-Hee Park Endowed Chair in Dentistry at UCLA and holds a joint appointment in the UCLA Department of Bioengineering, and his research team first developed a mouse model of head and neck squamous cell carcinoma that allowed them to identity the rare cancer stem cells present in HNSCC usingin vivolineage tracing, a method to identify all progeny of a single cell in tissues.

The researchers found that the cancer stem cells expressed the stem cell protein Bmi1 and had increased activator protein-1, known as AP-1, a transcription factor that controls the expression of multiple cancer-associated genes. Based on these new findings, the UCLA team developed and compared different therapeutic strategies for treating head and neck squamous cell carcinoma. They found that a combination of targeting cancer stem cells and killing the tumor mass, consisting of high proliferating cells, with chemotherapy drugs resulted in better outcomes.

The team further discovered that cancer stem cells were not only responsible for squamous cell carcinoma development, but that they also cause cervical lymph node metastasis.

This study shows that for the first time, targeting the proliferating tumor mass and dormant cancer stem cells with combination therapy effectively inhibited tumor growth and prevented metastasis compared to monotherapy in mice, said Wang, who is a member of the UCLA Jonsson Comprehensive Cancer Center and of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. Our discovery could be applied to other solid tumors such as breast and colon cancer, which also frequently metastasizes to lymph nodes or distant organs.

With this new and exciting study, Dr. Wang and his team have provided the building blocks for understanding the cellular and genetic mechanisms behind squamous cell carcinoma, said Dr. Paul Krebsbach, dean of the UCLA School of Dentistry. The work has important translational values. Small molecule inhibitors for cancer stem cells in this study are available or being utilized in clinical trials for other diseases. It will be interesting to conduct a clinical trial to test these inhibitors for head and neck squamous cell carcinoma.

Additional authors of the study include Demeng Cheng, first author and postdoctoral scholar in Wangs lab; Mansi Wu, Yang Li, Dr. Insoon Chang, Yuan Quan, Mari Salvo, Peng Deng, Dr. Bo Yu, Yongxin Yu, Jiaqiang Dong, John M. Szymanski, Sivakumar Ramadoss and Jiong Li who are all from the laboratory of molecular signaling in the division of oral biology and medicine at the UCLA School of Dentistry.

This work was supported in part by the National Institute of Dental and Craniofacial Research grants R37DE13848, R01DE15964 and R01DE043110.

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Targeting cancer stem cells improves treatment effectiveness and prevents metastasis - HealthCanal.com (press release) (blog)

Skin Stem Cells Comments Off on Targeting cancer stem cells improves treatment effectiveness and prevents metastasis – HealthCanal.com (press release) (blog) | March 10th, 2017

Robert Clayton Robbins, head of the Texas Medical Center, was named Tuesday as top choice for president of the University of Arizona.

The Board of Regents selected Robbins in Phoenix following interviews with him and one other candidate Monday.

Robbins will meet the campus community and the public at a forum Wednesday afternoon. The regents will vote next week formally to make him an offer, and contract negotiations will begin. A final vote on the contract is expected April 6, based on a timeline the regents released last week.

Robbins, who serves as president and chief executive officer at the Texas Medical Center, said at a press conference Tuesday he was eager to get on the road to Tucson. He said his top priority will be the UA's students.

"I look forward to meeting them, working with them, and helping them be prepared for this new world that were living in now," he said. "Its changing rapidly, and as the university family weve got to treat each one of them like our own children and help them be prepared for not just the four years they spend on campus, but the next 40 years of their life."

The announcement was delayed by more than an hour late Tuesday afternoon as members of the Board of Regents met privately to select their top candidate. Regent Bill Ridenour, who headed the search committee, said the delay was not a sign of disagreement.

"We just wanted to be very thorough," Ridenour said. "When you get nine people in a room that have differing thoughts, you want to make sure that you give those people every opportunity because its important, we think, that we be unanimous. So we are, and we are, and were excited."

Robbins is a cardiac surgeon who joined the Texas Medical Center as its president and CEO in 2012. In that time, he introduced five research initiatives centered on innovation, genomics, regenerative medicine, health policy and clinical research. The Texas Medical Center is the largest medical complex in the world, a press release said.

Dr. Robbins comprehensive experience as both a visionary leader and highly-respected physician, as well as his evident talent for advancing research, innovation, entrepreneurship and economic development will serve the University of Arizona and our state well, regents' President Eileen Klein said in a press release.

As a surgeon, Robbins has focused on acquired cardiac diseases with a special expertise in the surgical treatment of congestive heart failure and cardiothoracic transplantation. His research work includes the investigation of stem cells for cardiac regeneration.

The other finalist was Sethuraman Panch Panchanathan, executive vice president and chief research and innovation officer at Arizona State University.

Current UA President Ann Weaver Hart will step down after her successor is chosen. Hart will take a one-year sabbatical leave and return to the UA as a professor in the College of Education.

She became the university's first female president in 2012 and announced last year she would not seek renewal of her contract in 2018.

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Robert Clayton Robbins Top Choice for UA President - Arizona Public Media

Cardiac Stem Cells Comments Off on Robert Clayton Robbins Top Choice for UA President – Arizona Public Media | March 9th, 2017

An adult stem cell center established by the Kansas Legislature in 2013 is almost ready for its first clinical trial.

Buddhadeb Dawn, executive director of the Midwest Stem Cell Therapy Center, told legislators Tuesday that the trial will focus on treating graft-versus-host disease and will begin after final approvals from the U.S. Food and Drug Administration.

Our goal was to do this (trial) in January, but we got delayed because of different things, Dawn said during a hearing of the House Health and Human Services Committee. So we are now hoping to start it perhaps in summer.

Based at the University of Kansas Medical Center in Kansas City, the stem cell center has analyzed trials done elsewhere and hosted a clinical trial sponsored by a biotech company that uses modified stem cells from bone marrow to treat stroke.

But the graft-versus-host disease trial would be the first homegrown one.

Download the Midwest Stem Cell Therapy Center annual update to legislators.

Graft-versus-host disease is a potential complication when a patient receives a transplant of tissue, like an organ or bone marrow, from another person.

The disease occurs when transplanted tissue fights the patients natural immune system, potentially damaging the liver, skin or other areas. Its a rare illness, with about 20,000 cases in the United States each year.

Rep. Randy Powell, a Republican from Olathe, said the trial was a welcome and exciting development. He said his wife is at risk for the illness following treatment for leukemia.

I know that graft-versus-host is a big thing, Powell said. I think my wife still has an annual checkup where they keep their eye out (to make sure) thats not sticking its head up and causing issues.

Dawn said the center would like to take the next step and move into clinical trials using adult stem cells to treat things like joint ailments, diabetes and amyotrophic lateral sclerosis, also known as Lou Gehrigs disease.

But the regulatory process takes time.

Wed like to be able to offer a portfolio of different disease conditions that adult stem cells can benefit, Dawn said. Im hoping that within the next five years we would at least have some FDA approval for treatment with adult stem cells for other conditions.

Dawn said successful trials could lead to more private investment dollars so we are self-sustaining at some point in the future.

The centers reliance on state funds has been a point of contention for fiscally conservative legislators in the past. Most of the facilitys budget still comes from the states payment, which was reduced by about $28,000 to $754,500 last year.

Were maximizing every opportunity we can with what we have right now.

Thats far less than what stem cell research facilities in other states receive.

Doug Girod, executive vice president of the KU medical center, said that given the budget, Dawn and his small team have done remarkable work.

We could be 10 times bigger than we are and doing 10 times as much if we had the resources, Girod said. But I think were maximizing every opportunity we can with what we have right now.

The center was spearheaded by socially conservative legislators, including Sen. Mary Pilcher-Cook, to showcase adult stem cell research as an alternative to using stem cells derived from human embryos.

About $56,000 of its annual budget goes to educating the public about the differences between embryonic stem cells and adult cells and hosting an annual conference about advances in adult stem cell treatment.

Rep. John Wilson, a Democrat from Lawrence, said he initially was skeptical about the facility because he thought the Legislature was inserting itself into a religious or philosophical fight. But he said his attitude has changed.

Im glad that despite my opposition to it the state has gone forward with funding some really terrific research, Wilson said. My concern now is how do we take it to the next level so all of this hasnt been for nothing.

Andy Marso is a reporter for the Kansas News Service, a collaboration of KCUR, Kansas Public Radio and KMUW covering health, education and politics in Kansas. You can reach him on Twitter@andymarso. Kansas News Service stories and photos may be republished at no cost with proper attribution and a link back to kcur.org.

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Kansas Stem Cell Center Close To First Clinical Trial - KCUR

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March 8, 2017 by Thomas Bartosh, The Conversation Cancer cells, in red, cannibalize a type of stem cell, shown in green. The red cells with small specks of green are breast cancer cells that have eaten the stem cell.

Breast cancer death rates overall have steadily declined since 1989, leading to an increased number of survivors. But while breast cancer survivors are grateful their bodies show no trace of the disease, they still face anxiety. Breast cancer can and does return, sometimes with a vengeance, even after being in remission for several years.

By studying the "cannabilistic" tendency of cancer cells, my research team has made some progress in finding out why.

The chances of recurrence and disease outcome vary with cancer subtype. About one-third of patients diagnosed with triple negative breast cancer, the most aggressive subtype, may experience a recurrence in another part of the body. This is called distant recurrence.

It has been difficult, if not impossible, to predict if and when the same cancer will recur and to stop it. Recurrent disease may arise from just a single cancer cell that survived the initial treatment and became dormant. The dormancy allowed it to hide somewhere in the body, not growing or causing harm for an unpredictable amount of time.

Determining what puts these dormant cells to "sleep" and what provokes them to "wake up" and begin multiplying uncontrollably could lead to important new treatments to prevent a demoralizing secondary cancer diagnosis.

Recently, my research team and I uncovered several clues that might explain what triggers these breast cancer cells to go dormant and then "reawaken." We showed that cell cannibalism is linked to dormancy.

How do bone stem cells affect breast cancer?

Breast cancer can recur in the breast or in other organs, such as the lungs and bone. Where breast cancer decides to grow depends largely on the microenvironment. This refers to the cells that surround it, including immune cells, cells comprising blood vessels, fibroblasts and the select proteins they produce, among other factors.

Over a century ago, a surgeon named Stephen Paget famously compared the organ-specific prevalence of cancer metastasis to seeds and soil. Because breast cancer often relapses in bones, in this metaphor, which still holds forth today, the bone marrow provides a favorable microenvironment (the "soil") for dormant breast cancer cells (the "seeds") to thrive.

Thus, a substantial amount of recent work has involved trying to determine the role in cancer dormancy of a special type of cell, called mesenchymal stem cells (MSCs). These are found in bone marrow.

MSCs in bone marrow are highly versatile. They are able to form bone, cartilage and fibrous tissue, as well as cells that support the immune system and formation of blood. They are also known to travel to sites of tissue injury and inflammation, where they aid in healing.

Breast cancer cells readily interact with MSCs if they meet in the bone marrow. They also readily interact if the breast cancer cells recruit them to the site of the primary tumor.

My research team and I recently focused on potential outcomes of these cellular interactions. We found an odd thing happens, which may provide insight into how these breast cancer cells hide for a long time.

In the laboratory setting, we produced breast tumor models containing MSCs. We also re-created the hostile conditions that naturally challenge developing tumors in patients, such as localized nutrient deficits caused by rapid growth of cancer cells and overcrowding.

We discovered that cancer cells under this duress become dormant after eating, or "cannibalizing," the stem cells.

Our analysis provided compelling data demonstrating that the cannibalistic breast cancer cells did not form tumors as rapidly as other cancer cells, and sometimes not at all. At the same time, they became highly resistant to chemotherapy and stresses imposed by nutrient deprivation.

Dormant cells are widely linked to recurrence. We hypothesize that cannibalism thus is linked to recurrence.

What is cellular cannibalism, and why is it important in cancer?

Cellular cannibalism, in general, describes a distinct phenomenon in which one cell engulfs and eliminates neighboring, intact cells.

The percentage of cancer cells that show cannibalistic activity is relatively low, but it does appear to increase in more aggressive tumors.

There are several reasons breast cancer cells would want to eat other cells, including other cancer cells. It provides them with a way to feed when nutrients are in short supply. It also provides them a way to eliminate the very immune cells that naturally stop cancer growth. Cell cannibalism might also allow cancer cells to inherit new genetic information and, therefore, new and advantageous traits.

Notably, in our study, cannibalistic breast cancer cells that ate the stem cells and entered dormancy began to produce an array of specific proteins. Many of these proteins are also secreted by normal cells that have permanently stopped dividing, or senescent cells, and have been collectively termed the senescence-associated secretory phenotype (or SASP). Although cellular senescence is a part of aging, we are now realizing that it is also important for a variety of normal bodily processes, development of embryos and injury repair in adults.

This suggests that although dormant cancer cells do not multiply rapidly or form detectable tumors, they are not necessarily sleeping. Instead, at times they might be actively communicating with each other and their microenvironment through the numerous proteins they manufacture.

Overall, this might be a clever way for dormant cancer cells to "fly under the radar" and, at the same time, modify their microenvironment, making it more suitable for them to grow in the future.

Can cell cannibalism be exploited for diagnosis and treatment?

Although our results are promising, it's important to be cautious. While there appears to be a strong correlation between cell cannibalism and dormancy, for now we do not know if it is directly linked to cancer recurrence in patients. Studies are underway, however, to corroborate our findings.

Still, the fact that breast cancer cells cannibalize MSCs is intriguing. It provides an important foundation for developing new diagnostic tools and therapies. Indeed, we currently have several ways of applying our recent discoveries.

One exciting idea is to exploit the cannibalistic activity of cancer cells to feed them suicide genes or other toxic agents, using MSCs as a delivery vehicle, like a tumor-seeking missile.

Importantly, MSCs can be easily obtained from the body, expanded to large numbers in the laboratory, and put back into the patient. Indeed, they have already been used safely in clinical trials to treat a variety of diseases due to their ability to aid in tissue repair and regeneration.

A different avenue for drug development would involve keeping dormant cells in a harmless and nondividing state forever. It might also be possible to prevent cancer cells from eating the stem cells in the first place.

In our study, we were able to block cell cannibalism using a drug that targets a specific protein inside cancer cells. With this treatment approach, the cancer might essentially starve to death or be more easily killed by conventional therapies.

Explore further: A possible explanation for recurring breast cancer

This article was originally published on The Conversation. Read the original article.

In October, we mourned those who died of breast cancer and celebrated all of the women (and men) who have survived. What many of those survivors worry about, though, is that their breast cancer may come back. It has puzzled ...

Researchers from Mayo Clinic have quantified the numbers of various types of immune cells associated with the risk of developing breast cancer. The findings are published in a study in Clinical Cancer Research.

To understand what makes breast cancer spread, researchers are looking at where it lives - not just its original home in the breast but its new home where it settles in other organs. What's happening in that metastatic niche ...

New research explains how metastatic breast cancer cells might use bone marrow-derived mesenchymal stem cells (MSCs) to help them spread to bone tissue. A study using a 3D scaffold model has shown that breast tumor-derived ...

Scientists from the United States have made an important step toward eliminating cancer recurrence by combining immunotherapy with chemotherapy. Specifically, they found that chemotherapy alone leads to two types of dormant ...

A new study has identified a mechanism used by tumors to recruit stem cells from bone and convert them into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. This work, which pinpoints the specific biochemical ...

Research findings that first had scientists scratching their heads have turned out to be "quite revolutionary," according to study leaders at The Scripps Research Institute (TSRI).

For all the success of a new generation of immunotherapies for cancer, they often leave an entire branch of the immune system's disease-fighting forces untapped. Such therapies act on the adaptive immune system, the ranks ...

Mayo Clinic researchers have found that an experimental drug, LCL161, stimulates the immune system, leading to tumor shrinkage in patients affected by multiple myeloma. The findings are published in Nature Medicine.

Doctors may soon be able to detect and monitor a patient's cancer with a simple blood test, reducing or eliminating the need for more invasive procedures, according to Purdue University research.

Two key proteins involved in male breast cancer have been identified by University of Leeds scientists, potentially paving the way for more effective treatments.

A protein has been found to have a previously unknown role in the ageing of cells, according to an early study by Queen Mary University of London (QMUL). The researchers hope that the findings could one day lead to new treatments ...

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How 'cannibalism' by breast cancer cells promotes dormancy: A possible clue into cancer recurrence - Medical Xpress

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Stem cell therapy is a quickly advancing treatment being used across the country. Now, its becoming more prevalent in eastern North Carolina to those living with chronic pain an alternative to surgery. The minimally invasive procedure is showing results in alleviating back, knee, hip and shoulder pain. Though stem cell therapy is classified by the Food and Drug Administration as experimental, patients say theyre finding relief. Meet New Bern resident and a local endodontist Dr. Donnie Luper. He was skeptical of the procedure at first.

How did you know what those stem cells were going to differentiate into? I mean was I going to grow a foot out of my shoulder or something like that?

Luper tore his rotator cuff 25 years ago during a tubing incident on the Trent River. A subsequent fall during a golf trip in 2015 sent him to a specialist.

I went to see a shoulder surgeon in Richmond. He told me that he didnt think it was a complete tear of my rotator cuff, that I could probably have a minor surgical procedure done and I asked him about stem cell.

After talking with a friend who opted for stem cell treatment for her knee pain, Luper decided to find out more.

My option was if I would have had that shoulder surgery and they had do that bicep tendon repair, I mean I would have been in a sling for six weeks and probably not working for three months.

According to the Food and Drug Administration, stem cells sometimes called the bodys master cells - have the ability to divide and develop into many different cell types. Each new cell has the potential to remain a stem cell or become another type of cell, such as a nerve cell, a skin cell, or a red blood cell. They may also help repair the body by dividing to replenish cells that are damaged by disease, injury or normal wear. Parkinsons disease, spinal cord injuries, damaged organs and cancer could all be possibly treated with the use of stem cells, but more research is needed. Dr. Angelo Tellis is the owner/physician of Aegean Medical, which provides stem cell therapy to patients in Cary, Jacksonville, Morehead City and New Bern.

The adult stem cells we call multipotent stem cells so they can only differentiate into very specific or certain kinds of tissue. Whereas the embryonic stem cells we call pluripotent and can become a variety, almost any tissue. But I only deal with adult stem cells, theyre found to be more useful in clinical applications.

Dr. Tellis says adult stem cells are more responsive to growing tissue in very specific locations. When patients go into Dr. Tellis office for the two hour procedure, he starts by numbing an area of the abdomen and performing liposuction to collect one or two syringes of body fat.

Stem cells can be found in a lot of different tissues throughout the body, but theyre actually in one of the highest concentrations in your own body fat.

The stem cell sample is combined with platelet rich plasma or PRP collected through a blood draw.

That has a lot of the chemical signals and messengers that activate stem cells. So Ill typically combine that with some of the stem cells collected from the body fat and then go under x-ray guidance and put it exactly in the targeted location where we want to create that healing process.

Soreness and stiffness can be expected immediately following the procedure and for about a week after. Dr. Tellis says the results tend to improve with time, taking about three to six months for full recovery. This was Lupers experience in 2016.

Really didnt have to take any pain medications. The joint was really sore over the weekend just because of the injection of the fluid there and after that, I had a small amount of discomfort, but nothing I really had to take medication for.

After three months, Luper says he felt 90 percent better. But he decided to get a second opinion from a shoulder surgeon.

And he told me he thought the stem cells had done a lot but that I still had one little bone spur that was rubbing against the muscle and constantly tearing the little bit of the muscle.

After surgery, Luper says his left shoulder started feeling significantly better in about a month. He was also able to return to one of his favorite pastimes golf. While surgery helped eliminate all of his pain, Luper believes stem cells helped regenerate tissue that was damaged years ago.

He said my rotator cuff muscle didnt even look like it had been torn. I actually tore that, Im sixty now, and I actually tore that when I was 34, 35 tubing on the river and I had to do physical therapy for about three months, but he said he saw absolutely no evidence that Id ever had a rotator cuff tear.

Even though some have found relief and possibly a cure through stem cell therapy, the Food and Drug Administration has not approved any stem cell-based products for use, other than HEMACORD (HE-muh-cord). According to their website, the use of stem cells raises safety concerns such as excessive cell growth, the development of tumors as well as cells migrating from the site of administration and differentiating into inappropriate cell types. And then, theres the cost of the procedure, which is not covered by insurance. The price for the treatment ranges from $2,500 to $5,000. But for those who want to avoid major surgery and the downtime associated with recovery, the risk and cost may be worth it.

If Id have surgery, my deductible would have been that because I have an out-of-pocket max. And I would want to do anything to avoid surgery, especially something that would keep me out of work for three months.

The FDA recommends that consumers interested in stem cell therapy should start a conversation with their doctor about the potential risk to benefit ratio. In addition to Aegean Medical, Advanced Health and Physical Medicine in Greenville and Regenerative Medicine Clinic of Wilmington also provide stem cell therapy in eastern North Carolina.

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TiGenix has receivedpositive feedback from the FDA on an improved global phase III trial protocol for its lead candidateCx601 for Crohns disease. This is expected tospeed up US approval.

TiGenix is a Belgian companydevelopingstem cell therapies. The biotech is currently pushing its lead candidateCx601to the market for the treatment ofcomplex perianal fistulas in Crohns disease patients. Cx601 recently revealedpositive resultsin a European phase III study.

Following these results, the company submitted a number of technical adjustments for itspivotal phase III study for Biologics License Application (BLA) in the US, which were now approved by the FDA and are expected to acceleratethe process to US marketing authorization.

TiGenix is wellknown for its productChondroCellect, which was the first cell therapyto reach approval on the European market for the repair of knee cartilage.After the companyrecently withdrew its market authorization for this product, due to a lack of reimbursement, the biotech is focusing on its new leadCx601.

Thisproduct, currently awaiting EMA approval, consists ofallogeneic expanded adipose-derived stem cells (eASC), which are indicated for the treatment ofperianal fistulas in Crohns disease. The therapeuticeffects of eASCs are based on immunomodulatory abilities of these stem cells, which canrestore immune balance by suppressing a variety of immune cell subsets and inducing the generation of regulatory T cells.

Areas of the colon commonly affected duringCrohns disease

The current approval from the FDA will allow TiGenix to file the BLAbased on the efficacy and safety follow-up of patients at week 24, instead of week 52.The FDA has also agreed to accept fewer patients than originally planned in the study and endorsed a broader target population that will ultimately facilitate the recruitment process.

We believe that this revised protocol will allow us to file for approval one year earlier than we had originally plannedconcludedMaria Pascual, VP Regulatory Affairs & Corporate Quality of TiGenix

The current amendments will allow TiGenix to push its therapyto the US market even faster, which might pivotal for the company in light of its financial situation. After its shares had reached a low of22 cents back in 2013, the share price is currently still under 1. Withits low 34M IPO on Nasdaq in the end of last year, its market cap is stillonly at 191M. A low sum for a late stage clinical company.

As the EMAapproval forCx601 is expected soon, which will then be commercialized by Takeda, the company may actually be underestimated. The biotech recently started a new Phase Ib/IIa trial to testCx611 as a treatment for sepsis in patients with pneumonia.

Asecond platform consisting of transplanted allogeneic cardiac stem cells (AlloCSC)is currently in Phase II for acute myocardial infarction. It seems like TiGenix is definitely clinging toits position as one of the pioneers in stem cell-based therapies.

Images via shutterstock.com / CI Photos and CC 3.0 /RicHard-59

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Stem Cell Therapy receives FDA Boost to enter the US Market - Labiotech.eu (blog)

Cardiac Stem Cells Comments Off on Stem Cell Therapy receives FDA Boost to enter the US Market – Labiotech.eu (blog) | March 7th, 2017

A team of scientists has developed a new safety index for a common group of chemotherapy drugs, by using a stem cell model to screen such therapies for their potential to damage patients hearts.

The study, published in Science Translational Medicine, was co-authored by Paul Burridge, PhD, assistant professor of Pharmacology.

Tyrosine kinase inhibitors (TKIs), a class of chemotherapy drugs, have become increasingly important in treating many types of cancer. But almost all TKIs are also associated with cardiovascular side effects ranging from arrhythmias to heart failure and there has not yet been an effective tool to predict this cardiotoxicity.

In the current study, the scientists demonstrated that human-induced pluripotent stem cells can be used to model how TKIs might affect the hearts of patients receiving chemotherapy.

To do so, the scientists took stem cells from both a control group and patients with cancer and reprogrammed them to become cardiomyocytes, or heart muscle cells. Using high-throughput screening, they then evaluated how the heart cells responded to treatment with 21 different FDA-approved TKIs, looking at factors like cell survival, signaling and alterations in their ability to beat properly.

With the stem-cell data, the scientists were able to create a cardiac safety index, which ranks the TKIs on their likelihood of inflicting heart damage. That index correlates with the toxicity that has been observed in patients clinically a validation that suggests the screening system might be a powerful tool in predicting toxicity before therapies are ever administered to patients.

Future research could establish even more specific predictions, by comparing the genomes of patients who might experience a certain drug side effect, such as atherosclerosis, with those who dont. Long-term, what my lab is interested in is taking a patients whole genome and, based on the work weve done in the past, being able to predict whether a patient will have an adverse drug event, said Burridge, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. This is the whole idea of pharmacogenomics, or precision medicine: Everyone is going to have a different response to a drug, and that response good or bad is already encoded in all of us.

In the study, the scientists also discovered that administering insulin or insulin-like growth factor 1 alongside TKIs seemed to protect against some of the heart damage associated with the drugs. While its still early, this is the first step toward opening up a whole new field of identifying cardioprotectants to reduce the toxicity of these drugs, Burridge said.

The research was supported by the National Institutes of Health (NIH) grants K99/R00 HL121177, 14BGIA20480329, R01 HL132875, R01 HL130020, R01 HL128170, R01 HL123968, and R24 HL117756; the NIH Directors Pioneer Award; the American Heart Association Predoctoral Fellowship; the American Heart Association Beginning Grant-in-Aid; American Heart Association Grant-in-Aid; the American Heart Association Established Investigator Award; the National Science Foundation Graduate Research Fellowship; the Endowed Faculty Scholar Award of the Lucile Packard Foundation for Children and Child Health Research Institute at Stanford and Burroughs Wellcome Foundation Innovation in Regulatory Science.

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Using Stem Cells to Predict Toxicity of Chemotherapy Drugs - ScienceBlog.com (blog)

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People with a certain gene have an adverse reaction to the antiretroviral efavirenz

Liz HighleymanCorrespondent An HIV-positive bone marrow transplant recipient at the Mayo Clinic experienced prolonged viral remission lasting nearly 10 months longer than the so-called Boston patients after interrupting antiretroviral therapy (ART), according to a report at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) last month in Seattle.

Although his viral load eventually rebounded, his HIV reservoirs appeared to be reduced.

The only person known to be cured of HIV Timothy Ray Brown, known as the Berlin Patient stopped ART when he received a bone marrow transplant to treat leukaemia and has not had detectable virus for 10 years. Brown received a transplant from a donor with a double CCR5-delta-32 mutation, meaning they lack the CCR5 co-receptors most types of HIV use to enter T-cells.

It is unclear whether his sustained remission is attributable to the donors CCR5 mutation, the strong chemotherapy conditioning regimen used to kill off cancerous blood cells, a graft-versus-host reaction or multiple factors.

Bone marrow transplantation is apparently not sufficient to eradicate HIV.

A few years ago, Timothy Henrich reported on two HIV-positive bone marrow transplant patients in Boston who got stem cells from wild-type donors without the CCR5-delta-32 mutation, received a milder conditioning regimen and experienced acute graft-versus-host disease (GVHD). Both men maintained undetectable viral load longer than expected after interrupting ART, but eventually they experienced viral rebound at three and eight months after stopping HIV treatment.

The latest case, presented by Nathan Cummins of the Mayo Clinic in Rochester, Minnesota, and colleagues, involved a 55-year-old man who was diagnosed with HIV in 1990 and started combination ART in 1999 with a CD4 T-cell count of 300 cells/mm3. He stopped treatment between 2004 and 2009 for unexplained reasons, then restarted ART consisting of ritonavir-boosted atazanavir (Prezista) plus tenofovir disoproxil fumarate (DF) and emtricitabine (the drugs in Truvada).

In April 2013 the man was diagnosed with B-cell acute lymphoblastic leukaemia.

In anticipation of chemotherapy, his ART regimen was switched to raltegravir (Isentress), etravirine (Intelence), and tenofovir DF/emtricitabine. In October 2013 he underwent reduced intensity conditioning followed by an allogeneic stem cell transplant from a CCR5 wild-type donor.

At the time of transplantation the man had an HIV viral load of 25 copies/ml and a CD4 count of 288 cells/mm3, and he stayed on ART without interruption. After the transplant he developed opportunistic infections (E. coli septicaemia and pneumocystis pneumonia) and experienced GVHD at four months post-transplant.

The man continued on ART for more than two years after transplantation, mostly with detectable plasma viral load levels. HIV RNA was also undetectable in gut biopsy samples. HIV DNA in his peripheral blood cells became undetectable by day 56, and repeated leukapheresis procedures showed significant reductions in HIV RNA and DNA reservoir size.

In addition, that mans HIV antibody levels decreased, as indicated by weaker Western blot bands. However, single genome sequencing and phylogenetic analysis identified identical HIV clones at day 142, possibly due to homoeostatic proliferation, or replication of latently infected cells, while he had GVHD.

After having such low HIV levels for a prolonged period, the man underwent an analytic treatment interruption, or carefully monitored discontinuation of ART. His plasma HIV RNA levels were tested every two weeks for the first 12 weeks of ART interruption, then every four weeks.

At day 288 9,6 months after stopping ART he was found to have low-level viral rebound to 60 copies/ml. This rose to 1640 copies/ml by day 293, requiring that he restart HIV treatment.

The man had no evidence of drug resistance and his viral load was re-suppressed within a month.

Allogeneic peripheral blood stem cell transplantation in the setting of HIV is associated with significant reductions in HIV reservoir size by multiple measures, including prolonged combination ART-free remission, the researchers concluded.

They added that stem cell transplantation in the setting of suppressed viral replication may be associated with loss of HIV-specific immunity, and hypothesised that immune activation in the setting of GVHD without anti-HIV specific immunity may cause homoeostatic proliferation of latently infected cells, decreasing the chance of HIV eradication. http://www.aidsmap.com.

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Researchers report positive bone marrow transplant case - The Herald

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Rich Garton, CTV Windsor Published Tuesday, March 7, 2017 9:15AM EST Last Updated Tuesday, March 7, 2017 3:50PM EST

A Windsor infant with a rare genetic disorder has found a bone marrow match.

CTV Windsor first brought you Madalayna Ducharme's story a few months ago -- when her parents, Tamara and Charles made a plea for people to become bone marrow and stem cell donors.

It was on the heels of them learning Madalayna suffers from a rare genetic disorder called malignant infantile osteopetrosis. The side effects cause progressive vision and hearing loss, bone density and could potentially be fatal.

Doctors contacted the family this week and Ducharme is already undergoing treatment and is being prepped for the bone marrow transplant.

CTV News spoke with the family -- and they are elated with the news, but the Ducharme's excitement is tempered by a fear of what lies ahead.

We're a little scared at the same time because of the stuff she has to go through, says Tamara Ducharme. She has a regiment she has to go through before she can get this transplant.

That includes heavy doses of chemotherapy, with potential side effects, before a bone marrow transplant can take place.

Chemo is not going to be pretty, says Tamara Ducharme. She's a happy little girl, she cries once in a while like a regular child, she's going to be very ill and I don't know if I'm ready for that."

For now, they will borrow strength from their warrior princess.

Tamara Ducharme took to Facebook this morning to provide the good news. "We are sending big THANKS to all who have supported us, got swabbed, volunteered and donated blood," she posted.

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Windsor infant "warrior princess" finds a bone marrow match - CTV News

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Globalnews.ca

Could you save his life? Edmonton boy needs to find stem cell match Globalnews.ca Doctors say he needs a bone marrow transplant. Now, the family is desperately searching for a stem cell match. The world needs to know that this is what we need and this can save kids' lives, Mishio said. Not just Brady's life there's other ...

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Could you save his life? Edmonton boy needs to find stem cell match - Globalnews.ca

Bone Marrow Stem Cells Comments Off on Could you save his life? Edmonton boy needs to find stem cell match – Globalnews.ca | March 7th, 2017