Archive for the ‘Bone Marrow Stem Cells’ Category

Multiple sclerosis sufferer Roy Palmer is about to embark on the next phase of his pioneering treatment.

But it comes with risks he is prepared to take in the hope it will cure the debilitating condition.

The 43-year-old father of two from Quedgeley is determined it will work. He was diagnosed with relapsing remitting MS but now has the secondary progressive form of the disease, which means it gets steadily worse.

He said: I fought for a year to get hematopoietic stem cell transplantation and many people told me I didnt fit the criteria but I didnt let that stop me.

Mr Palmer had a week of injections to draw the stem cells from his bone marrow.

He and his wife Helen travelled to Hammersmith Hospital in London where he was given a day of chemotherapy.

Mr Palmer lost his hair as a result and was left feeling sick and tired.

The stem cells have been frozen and will be reintroduced to his body after another aggressive course of chemotherapy.

It will be fed directly into a main artery in his chest before Mr Palmer spends the next four weeks in isolation.

He will start the treatment on September 18 his 24th wedding anniversary.

Mr Palmer said: Im not someone to sit around and feel sorry for myself.

If the treatment works then, oh my God, I couldnt begin to describe what it would mean to me.

He added: To be able to walk out of my front door would mean the world.

I know Im lucky to be able to get the treatment. Im worried, my immune system will be obliterated, but I have to give this everything. Im a fighter and determined to make this work.

Mr Palmers family back his decision to undergo HSCT treatment, although they worry about the effect it will have.

His 45-year-old wife said: When they give the chemotherapy it brings the body back down to zero.

It will stop any immune system and take some time for the body to start getting back to normal.

When Roys levels are up they will start to reintroduce the stem cells.

The MS Society website says HSCT aims to reset the immune system to stop it attacking the central nervous system.

It uses chemotherapy to remove the harmful immune cells and then rebuilds the immune system using haematopoietic stem cells found in bone marrow.

They can produce all the different cells in the blood.

Mrs Palmer said: Im happy for Roy to take that risk and to support him but it is a lethal dose of chemo.

The treatment can be done abroad and costs around 60,000. In the past we were considering that option but there is no aftercare.

The couples daughter Abi, 12, said: I feel a little scared for dad but okay. I cant remember him walking.

And 20-year-old son Jack said: Dad has been in a chair for about 10 years and to see him walk again would mean everything.

Just standing next to each other would mean the world.

Once the stem cells are back in Mr Palmers body the hope is he will make a full recovery and be free of MS,

He said: It will be great to not have to ask people to do things for me.

I do what I can but I dont like to hang around waiting.

I want people to know there is treatment and it can be a fight but Ive got to do this now.

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MS sufferer gets pioneering stem cell treatment - Gloucestershire Live

It has been six years sinceSaskatchewan hockey playerMandi Schwartz died from acute myeloid leukemia, but her legacy lives on in anannual fundraising run in Saskatoon.

The Run for Mandistarts at 1 p.m. CST at River Landing on Sunday, and proceeds from the event go towards a foundation set up in Schwartz's name.

Her father, Rick Schwartz, said the event means a lot to thefamily.

"It's very special to know that your daughter has touched so many people's lives and we're happy to be a part of it," Schwartz told CBC Radio's Saskatchewan Weekend.

"But more importantly we're going to try save people's lives today and have a little bit of fun at the same time."

A new addition to this year's event will be the presence of the OneMatch stem cell and marrow network, which will be encouraging run participants to register as potential donors.

Mandi Schwartz was a star player with Yale University's women's hockey team. (Yale University)

A number of bone marrow recipients, including Regina boy Lincoln Honoway, will also be present at the event.

Schwartzsaid he wishesthere had been a way to save the life of his daughter, who was a starhockey playerat Yale University in the U.S.

He said he hopes Sunday's event will help encourage more people in Saskatchewanto sign up to the donor network.

"I've talked to people who have been donors," said Schwartz.

"There's no special gift or special feeling in their life as knowing that they've saved someone's life."

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Mandi Schwartz memorial run doubles as stem cell, marrow donor drive in Saskatoon - CBC.ca

Researchers are looking for ways eliminate the need for bone marrow donors altogether and instead use different types of cells derived from the patient in need of a transplant, says Dr Vladislav Sandler.

At the moment, people who develop leukaemia, lymphoma and otherblood diseases often need to undergo a hematopoietic stem cell transplantation (HSCT). This is because initial treatment of the disease (front-line therapy) often fails and the disease comes back.

Hematopoietic stem cells (HSC) are vital because they constantly regenerate the blood system giving rise (differentiating) into all types of blood cells such as red blood cells, white blood cells and platelets. Sometimes,patients get cells for the HSCT from close relatives (related allogeneic transplantation), who happen to be a match or by using donor data bases that can match them with strangers (unrelated allogeneic transplantation). The patients own HSC are wiped out with chemotherapy and replaced with donated blood-forming steam cells which create healthy new blood cells free from disease.

The patients own HSC are wiped out with chemotherapy and replaced with the donated blood-forming stem cells which createhealthy new blood cellsfree from disease.

Often, there is not a perfect match between a donor and a patient but physicians try and find the closest one possible. When a match is not perfect, a risk of rejection of the newly transplanted cells significantly grows. There are several teams of researchers trying to find a way to eliminate the need for bone marrow donors altogether and instead use different types of cells derived from the patient in need of a transplant.

This work, to directly reprogram the patients own cells to create hematopoietic stem cells, (from which all cellular blood components are derived) has been going on for some time and has had some success[1][2][3]. However, it is a very long and cumbersome process to produce HSC cells from a patients own cells and it looks like this may never be a practicable solution to the problem. We simply cant seem to be able to get the newly formed HSC cells to replicate into the sufficient number of cells needed to form a viable HSCT.

What I discovered when I was at Cornell University was that there is a small subset of postnatal hemogenic endothelial cells (Hu-PHEC) which survive in the liver and blood vessels of the umbilical cord and placenta into adulthood. It has been known for quite a while that in the fetus, similar cells produce first definitive HSC. It was accepted as a dogma that they either lose their ability to do this after birth or simply disappear. However, as it often happens in science, this was not entirely correct. Hu-PHEC can be isolated from postnatal tissues and made to generate HSCde-novo.

In animal experiments, we took purified and stimulated Hu-PHEC and transplanted them into immunocompromised mice.

What we found was that the transplanted cells did engraft and created a healthy new human blood system in the recipient mice. What seemed to happen was that by putting them back into circulation within the body reactivated their ability to produce HSC cells as they doin utero.

We dont yet understand the mechanism but we are working on this and we need to work out a way to get enough cells for human transplantation.

Development of Hu-PHEC technology would create an opportunity to get rid of bone marrow/HSC donations. We would no longer have to go to a donor or a family member, but simply harvest some of these special post-natal hemogenic endothelial cells from the patients own body.

Another area of our research has been to develop a conditioning product which helps eliminate the patients diseased HSC with minimal collateral damage to the rest of the body. At the moment, patients undergo a rather terrible process of preparation for a HSCT. It involves chemotherapy and radiation and can seriously harm various unrelated healthy cells. In some cases, patients do not survive the conditioning process. We have developed a type of immune therapy which is a bi-specific antibody that redirects patients own immune cells to only attack and kill HSC. It leaves other cells alone, so does not damage reproductive system. This should mean that men and women undergoing conditioning in advance of a bone marrow transplantion would not need to undergo fertility saving treatment (no need to freeze sperm or eggs). This bi-specific antibody, which is filed for a world-wide patent, is much less dangerous and detrimental to health than current treatment options. We have proved its effectiveness in animal trials, but we are now hoping to move on to Phase 1 clinical trials within the next two years.

[1]Sandler, V. M. et al. Reprogramming human endothelial cells to hematopoietic cells requires vascular induction. Nature 511, 312-318, doi:10.1038/nature13547 (2014).Validated in: Lis, R. et.al. Conversion of adult endothelium to immunocompetent hematopoietic stem cells. Nature Published online 17 May 2017, doi:10.1038/nature22326 (2017).

[2]Sandler V.M et al.Reprogramming of Embryonic Human Fibroblasts into Fetal Hematopoietic Progenitors by Fusion with Human Fetal Liver CD34+ Cells. PLoS ONE 6(4) 2011.

[3] Pereira C.F. et al. Induction of a hemogenic program in mouse fibroblasts. Cell Stem Cell. 2013 Aug 1;13(2):205-18.

Vladislav Sandler is the co-founder of HemoGenyx LLC, a US preclinical stage biotechnology company launching innovative new treatments for blood diseases using blood-forming (hematopoietic) stem cell transplantation (HSCT) techniques.

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Eliminating the need for bone marrow donors - The Hippocratic Post (blog)

It will take you just a few hours to donate stems cells but it will save someones life as it is usually the last or the only resort for those suffering from blood cancer. Stem cells are undifferentiated biological cells that can grow into specialized cells. There are two types of stems cells, which are embryonic stem cells and adult stem cells. Embryonic stem cells are extracted from theblastocyst, which is a structure that contains cell mass that develops into an embryo. Adult stem cells are the undifferentiated cells that replenish the dying cells or repair the damaged cells. These adult stems cells are donated during the stem cell donation. Stems cells are transferred to the patient, where it differentiates into healthy specialized cells. (ALSO READMajor blood types and who can donate blood to whom).

Stem cell donation is voluntarily donating the stem cells produced by your body. It can be donated in two ways. The first method is called Peripheral blood stem cell (PBSC) donation while the other method is bone marrow donation. Bone marrow donation requires hospitalization. Bone marrow is collected from your pelvis by doctors under general anesthesia using a syringe. You may experience pain and bruise but you will recover within a week.

Peripheral blood stem cell donation is used by 90 percent of the people to donate stem cells. It is an easy and quick process to collect the blood-forming cells found in the circulating blood. This non-surgical process of collecting the stem cells is called apheresis.

You need to register to donate stem cell. Your cell sample from cheek is analyzed for HLA typing and when there is a requirement for stem cell with your HLA type, you will get a notification. A complete health check-up is carried out to ascertain that you are fit to donate the stems cells. Once the check up is done, you will be given an injection called GCSF (Granulocyte Colony Stimulating Factor)to increase the stem cell present in your blood. This injection will be administered for five days and on the fifth day, the stem cells are collected. A tiny tube will be inserted in your arm and this tube is connected to a machine that will collect the stem cells. Your blood will pass through the machine. This procedure usually takes about five hours. You may experience flu like symptoms after donating the stem cells but it will soon subside.

Your cells will be given to those suffering from blood cancer and it could save the life of that person.

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What is stem cell donation: How does peripheral blood stem cell collection work? - India.com

The parents of a Saskatchewan-born Yale University hockey player are trying to connect more people with a bone marrow and stem cell network that could save lives.

Rick and Carol Schwartz will be in Saskatoon on Sunday for the sixth annual Run for Mandi named after their daughter Mandi Schwartz, who was diagnosed with acute myeloid leukemia in December 2008 and died in April 2011.

READ MORE: Could you save his life? Edmonton boy needs to find stem cell match

Officials from the OneMatch Stem Cell and Marrow Network, part of Canadian Blood Services, will take swabs from volunteers in hopes of connecting donors with patients who need stem cell transplants.

Its the first time the event will have on-site registration for the network.

Fewer than 25 per cent of people find a stem cell donor in their family and only 50 per cent find a match in the international network of donors, according to Blood Services.

Mandi never found one.

It was frustrating to know that. Its almost like we let her down, Rick Schwartz said.

In 2010, his daughter penned a letter, stating her hope that doctors would find her a life-saving match. She also hoped to increase the donor registry to help others.

If someone else in Mandis family needed a stem cell transplant, she wouldve been the first person to help out, her mother said.

I just know she would be front and centre in leading a drive if she were with us today, Carol Schwartz said.

Another registration drive in Mandis name happens annually at Yale University. So far, more than 6,000 people have registered and 37 have resulted in stem cell matches.

Ideal candidates are between the ages of 17 and 35 and meet certain health criteria.

If a person registers and matches with a person in need, its usually as easy taking blood, according to Run for Mandi co-organizer Bobbylynn Stewart.

Fifteen per cent of the time, they do require your bone marrow, said Stewart, who lost her mother to acute myeloid leukemia.

They go in through your hip and draw it through there, so its under anesthesia. Its about an hour-long process.

READ MORE: Run for Mandi raises over $20K for memorial bursary funds

Sundays event lasts from 1 p.m. to 4 p.m. and running isnt required.

Lincoln Honoway, who was three when he was admitted to Regina General Hospital last year with dangerously low blood counts, will be in attendance.

After finding a stem cell transplant, Lincolns blood cell counts have started to rise and stabilize.

The run is planned for River Landing, with pro hockey players Ryan Murray, JC Lipon and Brandon Gormley expected to be there.

Mandis brother, Jaden Schwartz of the St. Louis Blues, will attend as well.

2017Global News, a division of Corus Entertainment Inc.

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Family of Mandi Schwartz connecting donors with stem cell network - Globalnews.ca

Erica Honoway is scheduled to speak at the annual "Run for Mandi" charity event in Saskatoon, after her son Lincoln was saved by a bone marrow transplant.Michael Bell / Regina Leader-Post

An annual run honouring a late Canadian hockey player is working with a bone marrow and stem cell registry group in hopes of helping more people in her name.

The Run for Mandi is named for Saskatchewan hockey player Mandi Schwartz, who was diagnosed with acute myeloid leukemia in 2008 while she was part of the Yale Bulldogs hockey team. She died in 2011.

The event kicks off Sunday afternoon at River Landing. The five-kilometre run and the one-kilometre family walk will start at two, and for the first time a bone marrow and stem cell registry group will be set up at the run.

Mandis mother, Carol Schwartz, said shes proud of the work being done by the Mandi Schwartz Foundation in her daughters name.

It just makes these events more meaningful lives are being saved, Schwartz said. Theres probably no greater gift than meeting someone who got a successful match.

The OneMatch Stem Cell and Marrow Network, a part of Canadian Blood Services, will accept registrations at Sundays event. Schwartz said theyve handed out information before, but this is the first time OneMatch will swab volunteers at the event to register them in the network.

Bobbylynn Stewart with Breck Construction, the title sponsor for the event, said she has a personal stake in helping organize the run because her mother also died of acute myeloid leukemia. Its a chance for the company and the community to help other families with similar struggles, she said.

When you have a blood cancer or disorder, often times you are relying on a stem cell match through the network, Stewart said. So growing that network is vital.

Alongside the run will be a charity silent auction and a barbecue. Mandis brothers, professional hockey players Jayden and Rylan Schwartz, are also expected to attend, along with NHL players Ryan Murray and JC Lipton, and AHL player Brandon Gormley.

Erica Honoway, scheduled to speak before the run, said she is haunted by how close her family came to sharing in the Schwartzs tragedy.

Her son Lincoln was diagnosed with aplastic anemia last year, but a bone marrow transplant helped save his life.

In all the registries in the world, they found two matches for Lincoln, Honoway said. Every single person who gets on is another chance for someone to have their life saved.

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Annual 'Run for Mandi' hosting bone marrow registry to combat cancer - Saskatoon StarPhoenix

Madalayna and Tamara Ducharme, 33 days after Madalayna received her bone marrow transplant. Photo provided by Tamara Ducharme) By Adelle LoiselleAugust 25, 2017 5:10am

Six months ago, Windsor residents came out in droves to help baby Madalayna Ducharme find a bone marrow match.

On Saturday, they can help again by taking part in a bowl-a-thon dedicated to supporting the families of those who still need a transplant.

The 12th annual Bowling for Bone Marrow Bowl-a-Thon takes place Saturday at Rose Bowl Lanes on Dougall Ave. in Windsor. Check-in is at noon, and the fundraiser gets underway at 1pm.

It is the Katelyn Bedard Bone Marrow Associations biggest fundraiser of the year, and this year it can count Madalayna among its success stories.

The baby girl, who celebrated her first birthday this week, likes to dance and can stand while holding her parents fingers. Her mother, Tamara Ducharme is grateful for every day.

We were unsure if we were going to make it there, to the first birthday, she says. Were hoping that shell be a healthy little girl.

However, the struggle is not over. Friday, the family is driving up Hwy. 401 for Madalaynas six-month post-transplant appointment at Sick Kids Hospital in Toronto.

Ducharme says her daughter has bi-weekly hospital visits to ensure her medication is up to date. Madalayna still uses a feeding tube, and even months later, there is still the question whether the bone marrow transplant from her brother is working.

Theyll probably do an x-ray, says Ducharme about the upcoming appointment. Shes had a little growth. If her bones show changes that means shes on the track of getting better. Now, if there is no change, I dont know what were going to do.

Life with a young child who has received a transplant can also be very isolating, and Ducharme admits it has not been easy.

Were bubbled. We really go anywhere. We dont really play with other kids, she says. Youve gotta take the proper steps to take care of your child. If she could catch anything and it could be really detrimental.

She says the association has been very good to her family and they are grateful for their, and the communitys support over a challenging chapter in their lives.

Bryan and Joanne Bedard understand the difficulties faced by families of children waiting for a donor. They lost their 3-year-old daughter, Katelyn, in 2005 when they were unable to find one.

Since then, they have raised money for donor clinics and awareness of the OneMatch Stem Cell and Marrow Network which now has 6,500 registered donors. The Katelyn Bedard Bone Marrow Association has also donated $115,000 to stem cell and bone marrow transplant research at both the University of Windsor and the Universite de Montreal.

With files from Maureen Revait

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Bowl-A-Thon For Stem Cell Bone Marrow Transplant Recipients - BlackburnNews.com

NBC-5 News anchor Rob Stafford will return to the air Monday, after months of grueling treatment for a rare blood disorder that gave him a harrowing look at "my own mortality."

"I thought we'd get this thing nipped in the bud," said Stafford, 58, who took a leave of absence in March after being diagnosed to be in the early stages of amyloidosis.

Instead, Stafford said, he spent much of the last six months too sick to eat, drink or walk while learning that the road back to health from serious illness is a process.

"You learn that everybody reacts to these drugs differently and there is no guarantee of any outcome," he said.

Amyloidosis occurs when abnormal protein called amyloid is produced in bone marrow and can be deposited in tissues and organs. There are more than 40 types of the disorder that affect the heart, kidneys, liver, spleen, nervous system and digestive tract. Stafford's type known as light chain amyloidosis is rare, according to Dr. Ronald Go, Stafford's hematologist at the Mayo Clinic in Rochester, Minn.

Doctors had planned to remove or "harvest" stem cells from Stafford's own bone marrow and freeze millions of healthy ones. After wiping out the unhealthy cells using chemotherapy, Stafford was to have the healthy stem cells transplanted back into his bone marrow, where they were to reproduce themselves, Go said in March.

Zbigniew Bzdak/Chicago Tribune

Rob Stafford, shown Aug. 24, 2017, is planning to return to the anchor desk at NBC-5 News on Aug. 28 after months battling amyloidosis.

Rob Stafford, shown Aug. 24, 2017, is planning to return to the anchor desk at NBC-5 News on Aug. 28 after months battling amyloidosis. (Zbigniew Bzdak/Chicago Tribune)

But Stafford ran into several complications immediately after the transplant process began that forced him to remain hospitalized for most of March.

"There were times in the hospital when I thought he might not make it," said his wife, Lisa Stafford, who would jog around the Rochester area to alleviate her stress.

"On the runs, I would stop at every church to pray and light a candle."

Stafford returned to his home in Hinsdale in early April, too weak sometimes to walk across the room, drink a milkshake or even stay awake for the news, he said.

In June, test results showed the bone marrow transplant did not work as they had planned, and Stafford would need a new course of action to fight the disease, he said.

It was a terrifying place to be, Stafford said.

"You think, 'What if nothing works?'" he said. "I have clearly thought about my own mortality."

Doctors at Rush University Medical Center started Stafford on a new regimen of weekly chemotherapy, which dramatically improved his health. While he has not yet reached the low amyloid measurements that define remission, doctors are optimistic about his recovery and have cleared Stafford to return to work, he said.

Stafford will return to the 10 p.m. news. Dick Johnson and Patrick Fazio will share anchoring duties with Allison Rosati at 5 p.m. and 6 p.m. until Stafford is ready to return to those newscasts, said Frank Whittaker, station manager and vice president of news for NBC Chicago.

"We are eagerly looking forward to Rob's return on Monday night," Whittaker said in an email. "He has inspired all of us with his courage and determination over the past six months. It will be great to have him back in our newsroom."

Stafford said he remains grateful for the support he and Lisa felt from viewers, who sent him a steady stream of Facebook messages, cards and personal stories.

"It's like running a marathon, and there are all these people along the side cheering you on," Stafford said. "It helps you get through it."

vortiz@chicagotribune.com

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After treatment for serious illness, NBC-5 anchor Rob Stafford returning to air - Chicago Tribune

Bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces the ability to produce blood through induced proliferation. Credit: Professor Hitoshi Takizawa

It has been thought that only immune cells would act as the line of defense during bacterial infection. However, recent research has revealed that hematopoietic stem cells, cells that create all other blood cells throughout an individual's lifetime, are also able to respond to the infection. A collaboration between researchers from Japan and Switzerland found that bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces their ability to produce blood by forcibly inducing proliferation. These findings indicate that bacterial infections might trigger dysregulation of blood formation, such as that found in anemia or leukemia. This information is important to consider in the development of prevention methods for blood diseases.

Background: Bacterial Infection and the Associated Immune Reaction

When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use "sensors" on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.

Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout life. When infection occurs, a large number of immune cells are activated and consumed. It therefore becomes necessary to replenish these immune cells by increasing blood production in bone marrow. Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.

Proof: Hematopoietic Stem Cell Response to Bacterial Infection

Researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs. Lipopolysaccharide (LPS), one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsis, was given to laboratory animals to generate a bacterial infection model. Furthermore, researchers analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.

The results showed that LPSs spread throughout the body with some eventually reaching the bone marrow. This stimulated the TLR of the hematopoietic stem cells and induced them to proliferate. They also discovered that while the stimulus promoted proliferation, it also induced stress on the stem cells at the same time. In other words, although hematopoietic stem cells proliferate temporarily upon TLR stimulation, their ability to successfully self-replicate decreases, resulting in diminished blood production. Similar results were obtained after infection with E. coli bacteria.

Future Work

This study reveals that hematopoietic stem cells, while not in charge of immune reactions, are able to respond to bacterial infections resulting in a reduced ability to produce blood. This suggests that cell division of hematopoietic stem cells forced by bacterial infection induces stress and may further cause dysregulated hematopoiesis like that which occurs in anemia or leukemia. "Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs," said one of the study leaders, Professor Hitoshi Takizawa of Kumamoto University's IRCMS. "The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future."

This finding was posted online in Cell Stem Cell on 21 July 2017, and an illustration from the research content was chosen as the cover of the issue.

Explore further: Innate reaction of hematopoietic stem cells to severe infections

More information: Hitoshi Takizawa et al, Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.06.013

Journal reference: Cell Stem Cell

Provided by: Kumamoto University

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Bacterial infection stresses hematopoietic stem cells - Medical Xpress

Min Ma,1,* Shilin Chen,1,* Zhuo Liu,1 Hailong Xie,2 Hongyu Deng,3 Song Shang,1 Xiaohong Wang,4 Man Xia,5 Chaohui Zuo1

1Department of Gastroduodenal and Pancreatic Surgery, Laboratory of Digestive Oncology, Hunan Cancer Institute, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 2Institute of Cancer Research, South China University, 3Department of Laboratory Medicine, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 4Department of Molecular Medicine, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, 5Department of Gynecological Oncology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

*These authors contributed equally to this work

Abstract: Worldwide, gastric cancer (GC) is one of the deadliest malignant tumors of the digestive system. Moreover, microRNAs (miRNAs) of exosomes harbored within cancer cells have been determined to induce inflammatory conditions that accelerate tumor growth and metastasis. Interestingly, the oncogenic role of bone marrow mesenchymal stem cells (BM-MSCs) in the modulation of immunosuppression, tumor invasion, and metastasis was discovered to be partly mediated through the secretion of exosomes. In this article, high expression of miRNA-221 (miR-221) in exosomes of the peripheral blood was determined to be positively correlated with the poor clinical prognosis of GC, especially with respect to tumor, node, and metastases stage. Therefore, the expression of miR-221 in exosomes of the peripheral blood may be an important detection index for GC. Proliferation, migration, invasion, and adhesion to the matrix of GC BGC-823 and SGC-7901 cells were significantly enhanced by exosomes that originated from BM-MSCs that were transfected with miR-221 mimics. In conclusion, extracted exosomes from BM-MSCs transfected with miR-221 oligonucleotides can act as high-efficiency nanocarriers, which can provide sufficient miR-221 oligonucleotides to influence the tumor microenvironment and tumor aggressiveness effectively. Notably, the use of a miR-221 inhibitor with an excellent restraining effect in exosomes provides therapeutic potential for GC in future clinical medicine.

Keywords: exosomes, miR-221, BM-MSCs, gastric cancer, prognosis, oncogenic activity

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric ... - Dove Medical Press

TEL AVIV, Israel, Aug 21, 2017 /PRNewswire/ --BioLineRx Ltd. (NASDAQ: BLRX) (TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, announced today the filing of regulatory submissions required to commence a randomized, controlled Phase 3 registrational trial of BL-8040 for the mobilization of hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. The trial, named GENESIS, is expected to commence by the end of 2017, following receipt of regulatory approvals.

The Phase 3 GENESIS trial is aimed at evaluating the safety, tolerability and efficacy of the combination treatment of BL-8040 and granulocyte colony-stimulating factor(G-CSF), as compared to the control arm of placebo and G-CSF. The trial will be conducted in two parts: The first part, designed to validate the optimal dosing of BL-8040, is a lead-in, open-label, multi-center study that will include 10-30 patients, in order to assess the efficacy and safety of treatment with BL-8040 and G-CSF. This part will be followed by a randomized, placebo-controlled, multi-center study in approximately 180 patients. The primary endpoint will be the proportion of subjects mobilizing 6.0 x 106CD34+ cells/kg with up to 2 apheresis sessions in preparation for autologous transplantation after a single administration of BL-8040 and G-CSF, as compared to placebo and G-CSF.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, "We are excited to move forward with BL-8040 into a Phase 3 registration study. We have previously reported positive results supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen for rapid mobilization of stem cells. This represents a significant improvement over the current treatment, which requires four-to-eight daily injections of G-CSF and one-to-four apheresis sessions. We therefore hope that this Phase 3 trial will further support these results and help improve the standard of care for multiple myeloma patients."

"In parallel, we are continuing to expand the potential of our robust BL-8040 oncology platform, by advancing multiple clinical studies for additional indications that are ongoing or expected to commence during 2017. These include a large, randomized, controlled Phase 2b study in AML, as well as several Phase 2 combination studies with immune checkpoint inhibitors in solid tumors and hematological malignancies," added Mr. Serlin.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Stem Cell Mobilization

High-dose chemotherapy followed by stem cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), harvested from the peripheral blood by apheresis, and infused to the patient after chemotherapy. This type of treatment often replaces the use of traditional bone marrow transplantation, because the stem cells are easier to collect and the treatment allows for a quicker recovery time and fewer complications.

About BioLineRx

BioLineRx is a clinical-stage biopharmaceutical company focused on oncology and immunology. The Company in-licenses novel compounds, develops them through pre-clinical and/or clinical stages, and then partners with pharmaceutical companies for advanced clinical development and/or commercialization.

BioLineRx's leading therapeutic candidates are: BL-8040, a cancer therapy platform, which has successfully completed a Phase 2a study for relapsed/refractory AML, is in the midst of a Phase 2b study as an AML consolidation treatment and is expected to initiate a Phase 3 study in stem cell mobilization for autologous transplantation; and AGI-134, an immunotherapy treatment in development for multiple solid tumors, which is expected to initiate a first-in-man study in the first half of 2018. In addition, BioLineRx has a strategic collaboration with Novartis for the co-development of selected Israeli-sourced novel drug candidates; a collaboration agreement with MSD (known as Merck in the US and Canada), on the basis of which the Company has initiated a Phase 2a study in pancreatic cancer using the combination of BL-8040 and Merck's KEYTRUDA; and a collaboration agreement with Genentech, a member of the Roche Group, to investigate the combination of BL-8040 and Genentech's Tecentriq (Atezolizumab) in several Phase 1b/2 studies for multiple solid tumor indications and AML.

For additional information on BioLineRx, please visit the Company's website atwww.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events. BioLineRx industry updates are also regularly updated onFacebook,Twitter, andLinkedIn.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Some of these risks are: changes in relationships with collaborators; the impact of competitive products and technological changes; risks relating to the development of new products; and the ability to implement technological improvements. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 23, 2017. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contacts:PCG AdvisoryVivian CervantesInvestor Relations+1-212-554-5482rel="nofollow">vivian@pcgadvisory.com

or

Tsipi HaitovskyPublic Relations+972-52-989892rel="nofollow">tsipihai5@gmail.com

View original content:http://www.prnewswire.com/news-releases/biolinerx-announces-regulatory-submission-of-phase-3-registrational-study-for-bl-8040-in-stem-cell-mobilization-300506916.html

SOURCE BioLineRx Ltd.

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BioLineRx Announces Regulatory Submission of Phase 3 Registrational Study for BL-8040 in Stem Cell Mobilization - Markets Insider

There is truth in the old proverb about apple consumption and medical appointments. Insufficient vitamin C can contribute to leukemia. This observed relationship has now been shown to operate through the regulatory role the vitamin plays in the operation of bone marrow stem cells.

These days messages touting a single ingredient as being capable of curing all ills are more likely to peddleturmeric or cannabis, but a few decades ago it was vitamin C that was hailedas preventing everything from theflu to cancer if you took enough. As exaggerated as most of these claims were, it's certainly true that ascorbate, as it is also known, is vital to our health, sometimes in ways that are still unexplained.

We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we havent fully understood why, said Dr Sean Morrison of University of Texas Southwestern. Stem cells clearly played a part, but are so rare in any individual tissue that it is impossible to collect the millions usually used for metabolic analysis. Moreover, most mammals make their own ascorbate, but humans cannot, impeding the use of animal models.

Morrison and his co-authors of a paper published in Nature had to develop new techniques to measure metabolite usage in populations as small as 10,000 stem cells to address the first problem. On applying these techniques the authors discovered each type of blood-forming cell has a distinctive signature to its metabolite consumption. They tackled the second problem using mice that lack ascorbate-producing enzymes.

When given a low vitamin C diet these mice had more, and more active, bone marrow stem cells, increasing blood cell production at the price of higher rates of leukemia. The vitamin C concentration was related to levels of the enzyme Tet2, which regulates blood production. Without enough Tet2, the stem cells behaved like an overheating engine, turning out blood cells at a great rate until they turned cancerous. Something similar is observed when mutations reduce Tet2 production.

The first clinical application of the discovery is for patients with clonal hematopoiesis, a condition that often involves reduced Tet2 production and leukemia. Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement, Morrison said. These patients... need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer.

Since stem cells are much sparser in the rest of the body than in bone marrow it will be even more challenging to extend the research to other cancers.

The ideal dose of vitamin C remains to be established, although a paper, coincidentally published last week, may indicate benefits beyond current recommendations.

Read more:
Vitamin C Can Suppress Leukemia By Regulating Blood Cell Production - IFLScience

Representational image

Washington D.C. : A study has recently revealed that vitamin C may tell faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers.

According to researchers, certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia.

The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

Corresponding study author Benjamin G. Neel said, "We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies."

The results suggested that changes in the genetic code (mutations) that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre-leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia.

The study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the team genetically engineered mice such that the scientists could switch the TET2 gene on or off.

The findings indicated that vitamin C did the same thing as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukemia cancer stem cells from human patients implanted in mice.

"Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA," said first study author Luisa Cimmino.

"For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer," Cimmino added.

The findings appear in journal Cell.

See the article here:
Vitamin C may help genes to kill blood cancer stem cells - ETHealthworld.com

New parents are beginning to bank their babys cord blood cells in the hope that they can be used to treat serious diseases later on in the childs life.

Many of them have been told that the cells can already be used to treat about 80 blood and immunological conditions. So they fork out thousands a year for the service.

What they are not told is that the tiny amounts saved at birth would not be sufficient to treat a serious condition in an adult.

Stem cells are currently being used to treat

In the future, they are expected to help in the treatment of

Globally, around 50,000 cases of cancer have been treated with stem cells from cord blood, but banking is not a feasible solution because the amount preserved is not enough for bone marrow transplants in adults, says Dr Dharama Choudhary, bone-marrow transplant specialist at BLK Super Speciality Hospital.

For example, if one child has leukemia and has a newborn sibling, instead of using the cord blood doctors would rather wait for a couple of years and use the bone marrow of the younger child for transplant, adds Dr IC Verma, senior consultant of medical genetics and genomics at Delhis Sir Ganga Ram Hospital.

Even if you have enough, using cord blood cells is more costly and the recovery period is longer, Dr Choudhary adds.

FROM SOLO TO POOL

How umbilical cord stem cells are saved

Currently, cord blood is preserved in less than 1% of deliveries in urban centres, with the number being a higher 2% in private tertiary-care hospitals. The percentage is higher in Hyderabad, Bangalore and Pune, although we have not been able to ascertain the reason, says Upamannyue Roy Choudhury, CEO of CordLife India, a private cord blood bank.

The idea of public registries run by charitable organisations never really took off. That registry was meant so that anyone could purchase stem cells from a shared bank, but it has only about 5,000 units of cord blood banked across India. Private banks have about 500,000, says Mayur Abhaya, executive director at Life Cell International, one such private bank.

To help more people get treated using stem cells from cord blood, private banks should now promote sharing within their own pool, doctors add. We have underutilised assets, so pools would benefit people who have not banked cord blood, says Abhaya.

His company charges an initial fee of Rs 17,000 for the processing of banked cord blood and then Rs 4,000 a year for banking it. We have now started a sharing system where, for the same amount, the baby, its parents and both sets of grandparents can draw cord blood too from the shared pool at no extra cost, he says.

Life Cell estimates that even with the sharing of saved cord blood, utilisation would be only around 10%, because of the low incidence of the conditions that cord blood can be used to treat.

In the four months since starting the community pool, 99% of new customers have opted for the sharing model. We are now going back to older customers and trying to bring them into this pool as well, Abhaya says.

FRACTIONAL BENEFITS

Case study: Family matters

On average, only about 0.004% to 0.005% of people who store cord blood end up using it for their own treatment, says Dr Choudhary of BLK.

In addition to the problem of too little cord blood being harvested for treatment of serious diseases in adults, there is the issue of incorrect storage. Storage is not done correctly in many Indian banks. The cord blood is cryopreserved, and when it is thawed, the number of viable cells drops drastically, Dr Choudhary says.

Public cord blood banking, though, has a future. Storing cord blood in a public banking system, where it may be used by others in need, is more feasible, says Dr IC Verma. It will take another couple of decades before people will be able to meaningfully use their own cord blood.

Read more here:
Striking a cord: Is it worth saving stem cells? Yes, if you plan to share - Hindustan Times

Forever Labs, a startup in Y Combinators latest batch, is preserving adult stem cells with the aim to help you live longer and healthier.

Stem cells have the potential to become any type of cell needed in the body. Its very helpful to have younger stem cells from your own body on hand should you ever need some type of medical intervention, like a bone marrow transplant as the risk of rejection is greatly reduced when the cells are yours.

Mark Katakowski spent the last 15 years studying stem cells. What he found is that not only do we have less of them the older we get, but they also lose their function as we age.So, he and his co-founders Edward Cibor and Steve Clausnitzer started looking at how to bank them while they were young.

Clausnitzer banked his cells two years ago at the age of 38. So, while he is biologically now age 40, his cells remain the age in which they were harvested or as he calls it, stem cell time travel.

Steven Clausnitzer with his 38-year-old banked stem cells.

Stem cell banking isnt new. In fact, a lot of parents are now opting to store their babys stem cells through cord blood banking. But thats for newborns. For adults, its not so common, and theres a lot of snake oil out there, Clausnitzer cautions.

There are places offering stem cell therapy and Botox, he said.

Forever Labs is backed by a team of Ivy League-trained scientists with decades of experience between them. Jason Camm, chief medical officer for Thiel Capital, is also one of the companys medical advisors however, the startup is quick to point out it is not associated with Thiel Capital.

The process involves using a patented device to collect the cells. Forever Labs can then grow and bank your cells for $2,500, plus another $250 for storage per year (or a flat fee of $7,000 for life).

The startup is FDA-approved to bank these cells and is offering the service in seven states. What it does not have FDA approval for is the modification of those cells for rejuvenation therapy.

Katakowski refers to what the company is doing as longevity as a service, with the goal being to eventually take your banked cells and modify them to reverse the biological clock.

But that may take a few years. There are hundreds of clinical trials looking at stem cell uses right now. Forever Labs has also proposed its own clinical trial to take your stem cells and give them to your older cells.

Youll essentially young-blood effect yourself, Katakowski joked of course, in this case, youd be using your own blood made from your own stem cells, not the blood of random teens.

Read more here:
Forever Labs preserves young stem cells to prevent your older self ... - TechCrunch

Researchers at the Mayo Clinic and the University of Minnesota say theyre on the brink of a new era in cancer care one in which doctors extract a patients white blood cells, have them genetically engineered in a lab, and put them back to become personalized cancer-fighting machines.

The so-called CAR T cellular therapies are expected to receive federal approval this fall for certain rare blood cancers B-cell forms of lymphoma and leukemia. But scientists at the Minnesota institutions hope thats just the first step that will lead to better treatment of solid tumor cancers as well.

This is really the first approval of a genetically modified product for cancer therapy, said Dr. Jeffrey Miller, deputy director of the Masonic Cancer Center at the University of Minnesota. If the proof of concept works, he said, we might be on the right track to get away from all of that toxic chemotherapy that people hate.

Participating in industry-funded clinical trials, the Minnesota researchers hoped to determine if patients with leukemia or lymphoma would be more likely to survive if their own stem cells were extracted to grow cancer-fighting T-cells that were then infused back into their bodies.

One analysis, involving trials by Kite Pharmaceuticals at Mayo and other institutions, found a sevenfold increase in lymphoma patients whose cancers disappeared when they received CAR T instead of traditional chemo-based treatment.

I often tell patients that T-cells are like super robocops, said Dr. Yi Lin, a Mayo hematologist in Rochester. Were now directing those cells to really target cancer.

The U.S. Food and Drug Administration is widely expected this fall to approve CAR T products made by Kite and Novartis, which genetically engineer T-cells to target so-called CD19 proteins found on the surface of leukemia and lymphoma cells.

The side effects can be harsh, because the T-cell infusions trigger an immune system response that can produce fever, weakness, racing heart and kidney problems. Short-term memory and cognitive problems also have occurred. Brain swelling led to five deaths of cancer patients who took part in a CAR T trial by Juno Pharmaceuticals. The trial was shut down as a result.

Lin said brain swelling appeared mostly in adults with leukemia. For now, she expects Kites CAR T therapy to be approved for diffuse large B-cell lymphoma and the Novartis therapy to be approved for acute lymphoblastic leukemia in children. Federal regulations also might restrict CAR T for patients whose cancers survived traditional treatments.

Current practice to treat these cancers generally involves chemotherapy and radiation. Physicians then transplant stem cells, often from donor bone marrow, to regrow the patients immune systems, which are weakened in the process of treatment.

CAR T differs in that patients will receive infusions of their own T-cells, genetically modified, which their bodies will be less likely to reject.

Its individualized medicine, Lin said.

Im on my way

Before he tried CAR T at Mayo as part of a clinical trial, John Renze of Carroll, Iowa, had received two rounds of chemo, two rounds of radiation, and an experimental drug that did nothing to stop the spread of lymphoma.

After you fail about four times, you start to wonder if anything is going to work, the 58-year-old said.

At first, there was no room for him in the Mayo trial which has been a problem nationwide as desperate cancer patients have searched for treatment alternatives. But then he got the call one morning last summer while ordering coffee at his local cafe.

Can you get up here by one? the Mayo official asked.

Im on my way, Renze replied.

Even before federal approval comes through, researchers such as Miller are looking beyond the first-line CAR T therapies, and wondering if the approach can be used on solid tumors. Roughly 80,000 blood cancers occur each year in the U.S. that could be treated with CAR T, but the total number of cancers diagnosed each year is nearly 1.7 million.

The challenge is that solid tumors dont have the same protein targets as blood cancers. And T-cells would have to be more discriminating if infused to eliminate tumors in solid organs, Miller said. If you destroy normal lung tissue (along with lung cancer), thats not going to work, he said.

Mayo researchers are studying whether CAR T can work against multiple myeloma, a cancer of the bone marrow, while U researchers are exploring ways to better control the CAR T-cells after they are infused in cancer patients.

Researchers also are trying to understand whether CAR T produces memory in the immune system, so it knows to react if cancers resurface.

In addition, Miller is studying whether NK cells, which also play a role in the human immune system, can be genetically modified and infused instead of T-cells to target cancer. The body doesnt reject NK cells from donors as much, he said. So NK cells from donor bone marrow or umbilical cord blood could be collected and mass produced to potentially provide faster and cheaper treatments.

Like many breakthrough therapies, CAR T will be expensive, with a price likely to exceed $200,000 per patient. How insurers plan to cover it remains unclear. Blue Cross and Blue Shield of Minnesota is evaluating evidence regarding CAR Ts effectiveness, and will set a coverage policy after it receives FDA approval, said Dr. Glenn Pomerantz, Blue Cross chief medical officer.

A surge for Mayo?

Mayo expects a surge of hundreds of cancer patients per year if CAR T is approved, because it will initially be provided by large medical centers that have experience with the therapy and its side effects. The Rochester hospital is planning to add staff and space dedicated to CAR T.

Miller said the U is developing advice for referring doctors and hospitals statewide, so they know what to do if CAR T patients show up with complex symptoms.

They can be a bit delayed and you cant just keep people in the hospital to see if they develop these things, he said.

Renzes stem cells were taken last July, and his modified T-cells were put back a month later. He lost weight and felt sick for weeks, and had to drive three hours to Mayo for frequent checkups.

But as of last Aug. 31, the cancer had vanished.

Every three months, he returns to Mayo to make sure the cancer hasnt re-emerged. Then he returns to Carroll, where he owns farmland and car dealerships and dotes on his grandchildren.

For people like me that have already failed a bunch of times, youre happy to try anything, he said. I mean, what else would I have done?

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Mayo Clinic, University of Minnesota develop 'robocop' stem cells to fight cancer - Minneapolis Star Tribune

ARZ050-051-059>061-070>073-LAZ001>006-010>014-017>022-OKZ077-TXZ097-112-126-137-138-150>153-165>167-201300-/O.CON.KSHV.HT.Y.0009.000000T0000Z-170821T0000Z/Sevier-Howard-Little River-Hempstead-Nevada-Miller-Lafayette-Columbia-Union-Caddo-Bossier-Webster-Claiborne-Lincoln-De Soto-Red River-Bienville-Jackson-Ouachita-Sabine-Natchitoches-Winn-Grant-Caldwell-La Salle-McCurtain-Bowie-Cass-Marion-Gregg-Harrison-Rusk-Panola-Nacogdoches-Shelby-Angelina-San Augustine-Including the cities of De Queen, Nashville, Mineral Springs, Dierks, Ashdown, Hope, Prescott, Texarkana, Stamps, Lewisville, Bradley, Magnolia, El Dorado, Shreveport, Bossier City, Minden, Springhill, Homer, Haynesville, Ruston, Farmerville, Bernice, Mansfield, Stonewall, Logansport, Coushatta, Martin, Arcadia, Ringgold, Gibsland, Jonesboro, Monroe, Many, Zwolle, Pleasant Hill, Natchitoches, Winnfield, Colfax, Montgomery, Dry Prong, Clarks, Grayson, Columbia, Jena, Midway, Olla, Idabel,Broken Bow, Atlanta, Linden, Hughes Springs, Queen City, Jefferson, Longview, Marshall, Henderson, Carthage, Nacogdoches, Center, Lufkin, San Augustine, Hemphill, and Pineland936 PM CDT Sat Aug 19 2017...HEAT ADVISORY REMAINS IN EFFECT UNTIL 7 PM CDT SUNDAY...* EVENT...High pressure aloft across the area will allow for temperatures to climb into the middle to upper nineties. These temperatures along with low level moisture will produce heat indices of 105 to 109 degrees. * TIMING...Heat indices will be near 105 to 109 in the afternoon and early evening before lowering. * IMPACT...Precautions should be taken to prevent heat related illnesses, including limiting outdoor work activities to the morning before temperatures rise and early evening after the readings lower. PRECAUTIONARY/PREPAREDNESS ACTIONS...Take extra precautions if you work or spend time outside. Whenpossible, reschedule strenuous activities to early morning orevening. Take frequent rest breaks in shaded or air conditionedenvironments. Know the signs and symptoms of heat exhaustion andheat stroke. Wear light weight and loose fitting clothing whenpossible and drink plenty of water.Heat stroke is an emergency, call 9 1 1.A heat advisory means that a period of hot temperatures isexpected. The combination of hot temperatures and high humiditywill combine to create a situation in which heat illnesses arepossible. Drink plenty of fluids, stay in an air-conditionedroom, stay out of the sun, and check up on relatives andneighbors.&&$$

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Bone Marrow Transplant gives local cancer patient more time with his family - KTBS

WASHINGTON D.C: Good news! A study has recently revealed that vitamin C may tell faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers.

According to researchers, certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia.

The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

Corresponding study author Benjamin G. Neel said, "We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies."

The results suggested that changes in the genetic code (mutations) that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre-leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia.

The study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the team genetically engineered mice such that the scientists could switch the TET2 gene on or off.

The findings indicated that vitamin C did the same thing as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukemia cancer stem cells from human patients implanted in mice.

"Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA," said first study author Luisa Cimmino.

"For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer," Cimmino added.

The findings appear in journal Cell.

Read the original:
Vitamin C could help genes kill blood cancer stem cells - Economic Times

Digital Trends

Want to live longer? Forever Labs wants to help, using your stem cells Digital Trends Using a patented device, Forever Labs collects stem cells from your blood marrow, which the team calls a wellspring for stem cells that replenish your blood, bone, immune system, and other vital tissues. The whole process is said to take around 15 ...

Read this article:
Want to live longer? Forever Labs wants to help, using your stem cells - Digital Trends

Jaipur: Sawai Man Singh (SMS) Hospital is showing the way to treat various types of blood cancer and other blood-related disorders, including aplastic anaemia, myeloma, lymphoma, leukaemia and thalassemia.

Despite the higher risk of infections in ICUs, the hospital has not reported a single mortality. Some 19 patients have undergone autologous bone marrow transplant since 2009 at the hospital. Patients who have done the transplant are vulnerable to infections as they have to stay in post-operative care in ICUs for 14 to 54 days.

While the high dose of chemotherapy put patients at the risk of death, the rejection of graft (bone marrow) remains a major concern for doctors.

Though patients are given immunosuppressive medicines to deal with the risk of rejection, they make patients more immune-compromised which in turn make them more vulnerable to infections.

But despite all these risk factors, the hospital has not witnessed a single death of patients who have undergone autologous bone marrow transplant.

"We maintain high standards and follow protocol of ICUs. We do not allow anyone to enter the ICUs. One attendant with one patient is allowed, but we allow him to enter the ICU only after he changes his clothes completely and follows all norms in ICUs to minimise the risk of infection," said Dr Sandeep Jasuja, head of the department (medical oncology), SMS Medical College.

But still, 36% (7 patients) of these 19 patients contracted bacterial (due to Escherichia coli, enterobacter, pseudomonas), fungal and viral infections. However, the doctors brought the situation under control by providing them antibiotics and other drugs.

Read more here:
Bone marrow transplants: SMS leads the way - Times of India

The study suggests it may encourage blood cancer stem cells to die.

Researchers say Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers.

They explained that certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukaemia.

The new study, published online by the journal Cell. found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

Study corresponding author Professor Benjamin Neel, of the Perlmutter Cancer Centre in the United States, said: "We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies."

He said changes in the genetic code that reduce TET2 function are found in 10 per cent of patients with acute myeloid leukaemia (AML), 30 per cent of those with a form of pre-leukaemia called myelodysplastic syndrome, and in nearly 50 per cent of patients with chronic myelomonocytic leukaemia.

Such cancers cause anaemia, infection risk, and bleeding as abnormal stem cells multiply in the bone marrow until they interfere with blood cell production, with the number of cases increasing as the population ages.

Prof Neel said the study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the researchers genetically engineered mice such that the scientists could switch the TET2 gene on or off.

Similar to the naturally occurring effects of TET2 mutations in mice or humans, using molecular biology techniques to turn off TET2 in mice caused abnormal stem cell behaviour.

Prof Neel said, remarkably, the changes were reversed when TET2 expression was restored by a genetic trick.

Previous work had shown that vitamin C could stimulate the activity of TET2 and its relatives TET1 and TET3.

Because only one of the two copies of the TET2 gene in each stem cell is usually affected in TET2-mutant blood diseases, the researchers hypothesised that high doses of vitamin C, which can only be given intravenously, might reverse the effects of TET2 deficiency by turning up the action of the remaining functional gene.

They found that vitamin C did the same thing as restoring TET2 function genetically.

By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukaemia cancer stem cells from human patients implanted in mice.

Study first author Doctor Luisa Cimmino, of New York University Langone Health, said: "Interestingly, we also found that vitamin C treatment had an effect on leukaemic stem cells that resembled damage to their DNA.

"For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer."

The researchers found that the combination had an enhanced effect on leukaemia stem cells, further shifting them from self-renewal back toward maturity and cell death.

Dr Cimmino said the results also suggest that vitamin C might drive leukaemic stem cells without TET2 mutations toward death, given that it turns up any TET2 activity normally in place.

Corresponding author Professor Iannis Aifantis, also of NYU Langone Health, added: "Our team is working to systematically identify genetic changes that contribute to risk for leukaemia in significant groups of patients.

"This study adds the targeting of abnormal TET2-driven DNA demethylation to our list of potential new treatment approaches."

See the original post here:
Blood cancer: High doses of vitamin C could encourage stem cells ... - Express.co.uk

(HELENA) ExplorationWorks is hosting a Be The Match bone marrow donor drive this week at the Great Northern Town Center.

The drive is meantto support those in need of bone marrow or blood stem cell transplants around the world.

The bone marrow drive isbeing held in conjunction with the ExplorationWorks Kids Kicking Cancer Camp.

The camp is open to childrendirectly affected by cancer.

Campers had the opportunity to make a card for a Be the Match child who is currently undergoing or awaiting treatment.

According to ExplorationWorks Education Director Lauren Rivers, the camp wants kids to connect with the Be The Match kids on levels most children would not understand.

"Knowing someone else is fighting the same fight will hopefully be a healing activity for all of the kids involved, Rivers said.

John Philpott of Be the Match said that some of the Be The Match kids children are still waiting for a match.

There are still thousands of patients every year who have to hear their doctor say theres no match for you, Philpott said. One Montanan [donation] can mean the difference for one patient.

According to Be the Match, someone is diagnosed with blood cancer every three minutes and someonedies every ten minutesfrom not receiving a transplant.

The Marrow Donor Registry Drive will continue at ExplorationWorks from 10a.m. to 5p.m. on Friday, August 18 and from 12:30 p.m. to 3p.m. on Saturday, August 19.

Registration takes around 10 minutes to complete and only involves some paper work and a few cheek swabs.

You must be between the ages 18-44 in order to register.

For more information about bone marrow donation and how to register, click here.

See more here:
ExplorationWorks hosts bone marrow drive - KRTV Great Falls News

HELENA ExplorationWorks is hosting the Be The Match bone marrow donor drive this week at the Great Northern Town Center.

The drive is intended to support those in need of bone marrow or blood stem cell transplants around the world. Its being held in conjunction with ExplorationWorks Kids Kicking Cancer Camp.

The camp is open to children who are directly affected by cancer in their lives. Campers had the opportunity to make a card for Be the Match child who is currently undergoing or awaiting treatment.

Our hope is that the kids attending our camp will be able to connect with the Be The Match kids on a level most other children wouldnt understand. Knowing someone else is fighting the same fight will hopefully be a healing activity for all of the kids involved, said ExplorationWorks Education Director Lauren Rivers.

John Philpott of Be the Match said that sadly, some of the Be The Match kids children are still waiting to be matched with a donor.

There are still thousands of patients every year who have to hear their doctor say theres no match for you, said Phillpott, One Montanan [donation] can mean the difference for one patient.

According to Be the Match, someone is diagnosed with blood cancer every three minutes and every 10 minutes someone dies from not receiving a transplant.

The Marrow Donor Registry Drive will continue at ExplorationWorks from 10 a.m. to 5 p.m. Friday and from 12:30 to 3 p.m. on Saturday.

Registration takes around 10 minutes to complete and only involves some paper work and a few cheek swabs. You must be between the ages of 18 and 44 in order to register.

For more information about bone marrow donation and how to register click here.

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Bone marrow drive held at ExplorationWorks - KTVH

Ball-and-stick model of the L-ascorbic acid (vitamin C) molecule, C6H8O6, as found in the crystal structure. Credit: public domain

Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone Health, and published online August 17 in the journal Cell.

Certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia, say the authors. The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

"We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies," says corresponding study author Benjamin G. Neel, MD, PhD, professor in the Department of Medicine and director of the Perlmutter Cancer Center.

Changes in the genetic code (mutations) that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre-leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia. Such cancers cause anemia, infection risk, and bleeding as abnormal stem cells multiply in the bone marrow until they interfere with blood cell production, with the number of cases increasing as the population ages.

Along with these diseases, new tests suggest that about 2.5 percent of all U.S. cancer patients - or about 42,500 new patients each year - may develop TET2 mutations, including some with lymphomas and solid tumors, say the authors.

Cell Death Switch

The study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes. Every cell type has the same genes, but each gets different instructions to turn on only those needed in a given cellular context.

These "epigenetic" regulatory mechanisms include DNA methylation, the attachment of a small molecule termed a methyl group to cytosine bases that shuts down the action of a gene containing them.

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The back- and-forth attachment and removal of methyl groups also fine-tunes gene expression in stem cells, which can mature, specialize and multiply to become muscle, bone, nerve, or other cell types. This happens as the body first forms, but the bone marrow also keeps pools of stem cells on hand into adulthood, ready to become replacement cells as needed. In leukemia, signals that normally tell a blood stem cell to mature malfunction, leaving it to endlessly multiply and "self-renew" instead of producing normal white blood cells needed to fight infection.

The enzyme studied in this report, Tet methylcytosine dioxygenase 2 (TET2), enables a change in the molecular structure (oxidation) of methyl groups that is needed for them to be removed from cytosines. This "demethylation" turns on genes that direct stem cells to mature, and to start a count-down toward self-destruction as part of normal turnover. This serves as an anti-cancer safety mechanism, one that is disrupted in blood cancer patients with TET2 mutations, says Neel.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the research team genetically engineered mice such that the scientists could switch the TET2 gene on or off.

Similar to the naturally occurring effects of TET2 mutations in mice or humans, using molecular biology techniques to turn off TET2 in mice caused abnormal stem cell behavior. Remarkably, these changes were reversed when TET2 expression was restored by a genetic trick. Previous work had shown that vitamin C could stimulate the activity of TET2 and its relatives TET1 and TET3. Because only one of the two copies of the TET2 gene in each stem cell is usually affected in TET2-mutant blood diseases, the authors hypothesized that high doses of vitamin C, which can only be given intravenously, might reverse the effects of TET2 deficiency by turning up the action of the remaining functional gene.

Indeed, they found that vitamin C did the same thing as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukemia cancer stem cells from human patients implanted in mice.

"Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA," says first study author Luisa Cimmino, PhD, an assistant professor in the Department of Pathology at NYU Langone Health. "For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer."

Researchers found that the combination had an enhanced effect on leukemia stem cells, further shifting them from self-renewal back toward maturity and cell death. The results also suggest that vitamin C might drive leukemic stem cells without TET2 mutations toward death, says Cimmino, given that it turns up any TET2 activity normally in place.

"Our team is working to systematically identify genetic changes that contribute to risk for leukemia in significant groups of patients," says corresponding author Iannis Aifantis, PhD, professor and chair of the Department of Pathology at NYU Langone Health. "This study adds the targeting of abnormal TET2-driven DNA demethylation to our list of potential new treatment approaches."

Explore further: A tumor-suppressing gene can be harmful in some cancers

Journal reference: Cell

Provided by: NYU Langone Health / NYU School of Medicine

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Vitamin C may encourage blood cancer stem cells to die - Medical Xpress

Until last week, leukemia survivor Fengfeng (not his real name) knew almost nothing about the person who saved his life 13 years ago. Holding a bouquet of flowers, Fengfeng spotted a woman in her 40s. He rushed to her and hugged her. He sensed this was the person he had been waiting for.

Thirteen years ago, Fengfeng was a 15-year-old middle school student in Chongqing. He was diagnosed with chronic myeloid leukemia, a type of cancer affecting the blood-forming cells of the bone marrow.

He has no siblings, and half-match transplant techniques using a patient's parent as the donor had not matured yet. So the only hope was to find a close match outside the immediate family, the possibility of which was only one in 100,000.

Doctors found details of Han Lu, then a 32-year-old nurse at a Chongqing dental hospital, in the city's databank for China's marrow donor programme.

On a winter day in 2004, Han's stem cells were transplanted into Fengfeng's body, saving his life. It was the first unrelated donor stem cell transplant to treat chronic myeloid leukemia in Chongqing.

"I always had a wish after the transplant," Fengfeng said. "I wanted to say 'thank you' to my donor face to face."

However, like others in the same situation, they remained strangers, though they lived in the same city, as international practice and China's stem cell donation rules prohibit donors and recipients from meeting until at least a year after a successful transplant.

Han had long wished to meet Fengfeng, but the boy's health was not stable, making their meeting impossible until now.

They managed to exchange gifts with the help of the Chongqing Red Cross Society.

Fengfeng bought a necklace and a photography book for Han on a trip to Thailand, while Han turned a red cashmere sweater she owned into 25 knitted roses with red straws for stems as a gift for Fengfeng's 25th birthday.

"Cashmere signifies warmth and the red straws look like blood vessels," said Han, who felt gratified when she learned that Fengfeng survived and has had a happy life.

This year, Fengfeng asked the city's Red Cross to help arrange a meeting with his hero. After obtaining Han's consent, Fengfeng's dream came true.

According to Huang Gangyi, deputy director of the Chongqing databank for China's marrow donor programme, most stem cell recipients are unwilling to go public.

"They don't want others to know that they had the disease," Huang said. "But meetings can help people better understand stem cell transplants and raise awareness about the need for donors.

"Many people have misunderstandings about it, thinking transplants will be harmful to the donor's health."

Last year, China's marrow donor programme had more than 2.3 million potential donors, the Red Cross Society of China said in May. The programme has facilitated more than 6,000 hematopoietic stem cell donations for patients at home and abroad.

Moved by the story of Fengfeng and Han, many people have called Huang in the past week and asked how they can become potential cell stem donors.

Fengfeng had type O blood before the transplant. Eventually, his blood type changed to B, the same as Han's.

"She gave me a second chance at life, and now I have a lifelong friend and a new family member," Fengfeng said.

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Stem cell recipient, donor meet 13 years after transplant - AsiaOne