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Category Archives: Maryland Stem Cells

Patients' Own Genetically Altered Immune Cells Show …

Posted: October 19, 2015 at 5:48 pm

Monday, July 20, 2015

In recent years, immunotherapy has emerged as a promising treatment for certain cancers. Now this strategy, which uses patients own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable. The results appeared in a study published online today in Nature Medicine.

Patients received an infusion of altered immune cells known as T-cells roughly 2.4 billion of them after undergoing a stem cell transplantation of their own stem cells. In 16 of 20 patients with advanced disease, there was a significant clinical response. The scientists found that the T-cell therapy was generally well-tolerated and that modified immune cells traveled to the bone marrow, where myeloma tumors typically are found, and showed a long-term ability to fight the tumors. Relapse was generally associated with a loss of the engineered T-cells.

This study suggests that treatment with engineered T-cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma, says first author Aaron P. Rapoport, MD, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine. Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.

The trial is the first published use of genetically modified T-cells for treating patients with multiple myeloma. The approach has been used to treat leukemia as well as lymphoma, according to Dr. Rapoport, who is the Director of the Blood and Marrow Transplant Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

More than 77,000 people in the United States have multiple myeloma, with about 24,000 new cases diagnosed each year. Patients are treated with chemotherapy and in many cases an autologous stem cell transplant, but long-term response rates are low, and median survival is three to five years.

The majority of patients who participated in this trial had a meaningful degree of clinical benefit, Dr. Rapoport notes. Even patients who later relapsed after achieving a complete response to treatment or didnt have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years.

The research is a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania and Adaptimmune, a clinical stage biopharmaceutical company which owns the core T-cell receptor technology and funded the study. Dr. Rapoport and co-authors Edward A. Stadtmauer, MD, of the University of Pennsylvania Abramson Cancer Center, and Gwendolyn K. Binder-Scholl, PhD, of Adaptimmune, contributed equally to the research. Dr. Rapoport is the studys principal investigator.

In the clinical study, patients T-cells were engineered to express an affinity-enhanced T-cell receptor (TCR) specific for a type of tumor antigen, or protein, known as a cancer-testis antigen (CT antigen). The target CT antigens were NY-ESO-1 and LAGE-1. Up to 60 percent of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which correlates to tumor proliferation and poorer outcomes. According to Adaptimmune, the trial is the first published study of lentiviral vector mediated TCR gene expression in humans.

Of the 20 patients treated, 14 (70 percent) had a near complete or complete response three months after treatment. Median progression-free survival was 19.1 months and overall survival was 32.1 months. Two patients had a very good partial response three months post treatment. Half the patients were treated at the University of Maryland Greenebaum Cancer Center and half at the University of Pennsylvania Abramson Cancer Center. Researchers note that the response rate was better than would be expected for a standard autologous stem cell transplant. In addition, patients did not experience side effects which have been associated with another type of genetically engineered T-cells (chimeric antigen receptors, or CARS) used to treat other cancers.

The study was originally developed by Carl H. June, MD, of the University of Pennsylvania Abramson Cancer Center, and Dr. Rapoport, who have been research collaborators for 18 years.

Multiple myeloma is a treatable but largely incurable cancer. This study reveals the promise that immunotherapy with genetically engineered T-cells holds for boosting the bodys ability to attack the cancer and provide patients with better treatments and control of their disease, says E. Albert Reece, MD., PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry.

The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States. It continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Marylands Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. medschool.umaryland.edu/

The University of Maryland Marlene and Stewart Greenebaum Cancer Center, a National Cancer Institute-designated center in Baltimore affiliated with the University of Maryland Medical Center and University of Maryland School of Medicine, offers a multidisciplinary approach to treating all types of cancer and has an active cancer research program. It is ranked in the top 50 cancer programs in the nation by U.S. News & World Report. http://www.umgcc.org.

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Maryland Stem Cell Research Fund: Funding Opportunities

Posted: July 2, 2015 at 12:54 am

Pre-Clinical & Clinical Grants is soliciting applications from companies to Advance Medical Therapies in Maryland.

A single Pre-Clinical Application may request up to $500,000 of direct costs, and a Clinical Application may request up to $750,000 of direct costs both cases for up to three years project.

Investigator-Initiated Grants is soliciting applications for Investigator-Initiated Research, which are designed for investigators with preliminary data supporting the grant application.

A single Application for an Investigator-Initiated Research Grant may request up to $600,000 of direct costs, for up to three years project.

Exploratory Research Grants is soliciting applications for Exploratory Research, which are designed for investigators who are new to the stem cell field and for exploratory projects without preliminary data.

A single Application for Exploratory Research Grant may request up to $100,000 of direct costs in any single year, for up to two years.

Post-Doctoral Fellowship Grants is soliciting nationwide applications from exceptional pre-doctoral students and post-doctoral fellows who wish to conduct research on human stem cells in the State of Maryland.

Each Fellowship will be up to $55,000 per year, for up to two years.

CIRM Collaboration for RFAs

Pertaining to Investigator-Initiated Research Grant Applications and Exploratory Research Grant Applications

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Maryland Stem Cell Research Fund: Funding Opportunities

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MRI based on a sugar molecule can tell cancerous from noncancerous cells

Posted: March 27, 2015 at 5:56 pm

Imaging tests like mammograms or CT scans can detect tumors, but figuring out whether a growth is or isn't cancer usually requires a biopsy to study cells directly. Now results of a Johns Hopkins study suggest that MRI could one day make biopsies more effective or even replace them altogether by noninvasively detecting telltale sugar molecules shed by the outer membranes of cancerous cells.

The MRI technique, so far tested only in test tube-grown cells and mice, is described in a report published March 27 in the online journal Nature Communications.

"We think this is the first time scientists have found a use in imaging cellular slime," says Jeff Bulte, Ph.D., a professor of radiology and radiological science in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. "As cells become cancerous, some proteins on their outer membranes shed sugar molecules and become less slimy, perhaps because they're crowded closer together. If we tune the MRI to detect sugars attached to a particular protein, we can see the difference between normal and cancerous cells."

Bulte's research builds on recent findings by others that indicate glucose can be detected by a fine-tuned MRI technique based on the unique way it interacts with surrounding water molecules without administering dyes. Other researchers have used MRI but needed injectable dyes to image proteins on the outside of cells that lost their sugar. In this study, Bulte's research team compared MRI readings from proteins known as mucins with and without sugars attached to see how the signal changed. They then looked for that signal in four types of lab-grown cancer cells and detected markedly lower levels of mucin-attached sugars than in normal cells.

Xiaolei Song, Ph.D., the lead author on the study and a research associate in Bulte's laboratory, explains that this is the first time a property integral to cancer cells, rather than an injected dye, has been used to detect those cells. "The advantage of detecting a molecule already inside the body is that we can potentially image the entire tumor," she says. "This often isn't possible with injected dyes because they only reach part of the tumor. Plus, the dyes are expensive."

Bulte cautions that much more testing is needed to show that the technique has value in human cancer diagnosis. His team's next step will be to see if it can distinguish more types of cancerous tumors from benign masses in live mice.

If further testing does show such success, Bulte and Song suggest the technique could be used to detect cancer at an early stage, monitor response to chemotherapy, guide biopsies to ensure sampling of the most malignant part of a tumor and eventually make at least some biopsies unnecessary.

Other authors on the paper are Raag D. Airan, Dian R. Arifin, Amnon Bar-Shir, Deepak K. Kadayakkara, Guanshu Liu, Assaf A. Gilad, Peter C.M. van Zijl and Michael T. McMahon, all of The Johns Hopkins University.

This project was supported by the National Institute of Biomedical Imaging and Bioengineering (grant numbers R01 EB015032 and R01 EB015031), the National Cancer Institute (grant number U54 CA151838), the Maryland Stem Cell Research Foundation (grant number MSCRFII-0042), and the Pearl and Yueh-Heng Yang Foundation.

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MRI based on a sugar molecule can tell cancerous from noncancerous cells

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MD Stem Cells Release Optic Nerve Vision Loss Reversed …

Posted: March 22, 2015 at 1:07 pm

January 24, 2013 -- MD Stem Cells helps nearly blind car accident victim regain her sight in Florida and see her mothers face again- other neurologic benefits reported as well.

Stefany had been in a motor vehicle accident in January 2012 and suffered severe head trauma. To help minimize swelling and damage to her brain, she had been placed in an induced medical coma. Tragically when she finally awoke, the beautifully clear vision she had taken for granted all her life was now nearly gone. The trauma had caused compression on her optic nerves and her world was now dark. She could barely see things a few inches in front of her face.

While she improved a bit over the next few months, her walking and balance were still very bad and her vision was still awful. Everything was terribly blurry and she could not distinguish faces. She and her family began searching for solutions and found MD Stem Cells.

Stefanys sister Valerie was our major contact explained Dr. Levy, President of MD Stem Cells. We talked about options and the new dual injection technique MD Stem Cells helped develop using Bone Marrow Derived Adult Stem Cells (BMSC) and the possibility of intravitreal stem cells in addition to the injections adjacent to the optic nerves. Stefanys vision was extremely poor and she understood that although other patients with optic nerve damage had improved following treatment, we could not be certain how she might respond. Treatment was provided in Florida in the United States.

I was feeling a bit nervous before going into the procedure, but the staff did make it easier for me to feel comforted including Dr. Levy, because he explained everything step by step recalls Stefany. When I opened my eyes I noticed that I could see my moms face from afar, before that would not have been possible.

Valerie, who is planning on attending nursing school, reports that even within a week of treatment her sisters vision has improved significantly and she can now count fingers several feet away. She also notes another unexpected improvement- Stefany is now walking without help much of the time and her balance is much improved. Stefanys mother also reports that she is speaking more clearly following the stem cell procedure.

We do not have an exact explanation for these reported neurologic improvements following the optic nerve treatment. There have been studies of Bone Marrow Adult Stem Cells, otherwise known as human mesenchymal stem cells (hMSCs), causing recovery of neurologic function in murine models of Multiple Sclerosis (MS). Its possible Hepatocyte Growth Factor (HGF), recently identified as responsible for suppressing those unwanted autoimmune responses and accelerating neuron myelin cell repair, may be of value following neurologic trauma reasoned Dr. Levy.

Stefany is very happy no matter the explanation for her improvements. I understood it would take four to six months to see major improvements and here I was finally able to see my moms face more clearly exclaimed Stefany, Thanks to this I am one step closer to accomplishing all my life goals and dreams.

MD Stem Cells is a trusted source of the latest information regarding clinically available adult stem cell treatments, coordinates patient referrals and manages the treatment process for patients and providers.

Website: http://www.mdstemcells.com Follow us on Twitter: @mdstemcells.

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TiGenix: TiGenix reports its full year 2014 results

Posted: March 18, 2015 at 2:56 am

Regulated information PRESS RELEASE

TiGenix reports its full year 2014 results

Leuven, Belgium - 17 March, 2015 - TiGenix NV (Euronext Brussels: TIG), an advanced biopharmaceutical company focused on developing and commercialising novel therapeutics from its proprietary platform of allogeneic, expanded adipose-derived stem cells, or eASC's, in inflammatory and autoimmune diseases, reported its results for 2014 today.

Business highlights

Strategic refocusing successfully completed

All resources focused on advancing the allogeneic expanded adipose-derived stem cell (eASCs) product pipeline. ChondroCelect marketing and distribution rights licensed to Sobi and Dutch manufacturing facility sold to PharmaCell

Management team strengthened with the appointment of Chief Medical Officer and VP Medical Affairs & New Product Commercialisation

Patient recruitment of Cx601 European Phase III study completed

Cx601 development for the United States progressed according to plan

Phase III trial design submitted to the Food and Drug Administration (FDA) for a Special Protocol Assessment (SPA)

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TiGenix: TiGenix reports its full year 2014 results

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Gene regulatory path revealed as target for therapy of aggressive pediatric brain cancer

Posted: March 10, 2015 at 2:54 am

Laboratory studies suggest anticancer drug already in clinical trials in children may interrupt this gene pathway

Working with cells taken from children with a very rare but ferocious form of brain cancer, Johns Hopkins Kimmel Cancer Center scientists have identified a genetic pathway that acts as a master regulator of thousands of other genes and may spur cancer cell growth and resistance to anticancer treatment.

Their experiments with cells from patients with atypical teratoid/rhabdoid tumor (AT/RT) also found that selumetinib, an experimental anticancer drug currently in clinical trials for other childhood brain cancers, can disrupt part of the molecular pathway regulated by one of these factors, according to a research team led by Eric Raabe, M.D., Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine.

AT/RT mostly strikes children 6 and younger, and the survival rate is less than 50 percent even with aggressive surgery, radiation and chemotherapy, treatments that can also disrupt thinking, learning and growth. AT/RT accounts for 1 percent of more than 4,500 reported pediatric brain tumors in the U.S., but it is more common in very young children, and it represents 10 percent of all brain tumors in infants.

"What's exciting about this study is that it identifies new ways we can treat AT/RT with experimental drugs already being tested in pediatric patients," Raabe says. Because few outright genetic mutations -- and potential drug targets -- have been linked to AT/RT, Raabe and his colleagues turned their attention to genes that could regulate thousands of other genes in AT/RT cancer cells. Experiments in fruit flies had already suggested a gene known as LIN28 could be important in regulating other genes involved in the development of brain tumors. Specifically, the LIN28 protein helps regulate thousands of RNA molecules in normal stem cells, giving them the ability to grow, proliferate and resist damage.

"These factors provide stem cells with characteristics that cancer cells also have, such as resistance to environmental insults. These help tumor cells survive chemotherapy and radiation," says Raabe. "These proteins also help stem cells move around the body, an advantage cancer cells need to metastasize."

In a report on one of their studies, published Dec. 26 in the journal Oncotarget, the researchers examined cell lines derived from pediatric AT/RT patients and the tumors themselves. They found that the two members of the LIN28 family of genes were highly expressed in 78 percent of the samples, and that blocking LIN28 expression with specially targeted gene silencers called short hairpin RNAs curbed the tumor cells' growth and proliferation and triggered cell death. When Raabe and colleagues blocked LIN28A in AT/RT tumor cells transplanted into mice, they were able to more than double the mice's life span, from 48 to 115 days.

Using selumetinib in cell line experiments, the scientists cut AT/RT tumor cell proliferation in half and quadrupled the rate of cell death in some cell lines. Raabe says the drug appeared to be disrupting a key molecular pathway controlled by LIN28.

In a second study, described in the Journal of Neuropathology and Experimental Neurology, Raabe and his colleagues examined another factor in the LIN28 pathway, called HMGA2, which is also highly expressed in AT/RT tumors. They again used short pieces of RNA to "silence" HMGA2, which led to lower levels of cell growth and proliferation and increased cell death. Blocking HMGA2 also doubled the survival rate of mice implanted with tumors derived from pediatric AT/RT cell lines from 58 to 153 days.

Raabe says his team's work with LIN28 and HMGA2 should not only lead to understanding why cancers like AT/RT are so aggressive, but "also identify their Achilles' heels. We have shown that if we target these key proteins downstream of LIN28 in AT/RT, the tumors unravel."

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Gene regulatory path revealed as target for therapy of aggressive pediatric brain cancer

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American Spine offers experimental fix for pain — Gazette.Net

Posted: January 28, 2015 at 1:57 pm

Doctors at American Spine in Germantown and throughout the State of Maryland have rolled out a new experimental set of regenerative treatments for injuries ranging from torn muscles to serious back pain and patients are starting to take notice.

Frank Chilcoat received his first platelet rich plasma injection on Dec. 2 for what he described as, Two tears on the outer part of my shoulder in the muscle.

Ive actually seen some difference already, Chilcoat said. My range of motion was very bad. I was limited and I would get pain.

Platelet rich plasma injections and stem cell therapies are under American Spines umbrella term of Regenerative Medicine Therapy, which the practice describes as the application of biological therapies that enhance the bodys ability to heal itself.

American Spine has several different locations, including one in Olney and another in a brand new building in Germantown, which will be a fully functioning surgical facility. As of now, any of the surgical locations can offer the regenerative treatments on site.

Dr. Mike Yuan has been spearheading the procedures at American Spine.

The [platelet rich plasma] procedure is a very simple process. Draw blood, like a blood test, then centrifuge the blood, Yuan said, explaining that the centrifuge separates the components of the blood isolating the plasma that helps bodies heal.

Next, doctors inject the patients own plasma back into the problem area, focusing their healing functions directly on site.

Instead of waiting for your body to take it to the site, we are injecting there, Dr. Sandeep Sherlekar, a co-owner of American Spine, said.

This procedure uses the bodys natural method of healing in a more effective way, giving the body the green light to send more healing cells to help out.

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American Spine offers experimental fix for pain -- Gazette.Net

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American Spine offers experimental fix for pain

Posted: January 28, 2015 at 1:57 pm

Doctors at American Spine in Germantown and throughout the State of Maryland have rolled out a new experimental set of regenerative treatments for injuries ranging from torn muscles to serious back pain and patients are starting to take notice.

Frank Chilcoat received his first platelet rich plasma injection on Dec. 2 for what he described as, Two tears on the outer part of my shoulder in the muscle.

Ive actually seen some difference already, Chilcoat said. My range of motion was very bad. I was limited and I would get pain.

Platelet rich plasma injections and stem cell therapies are under American Spines umbrella term of Regenerative Medicine Therapy, which the practice describes as the application of biological therapies that enhance the bodys ability to heal itself.

American Spine has several different locations, including one in Olney and another in a brand new building in Germantown, which will be a fully functioning surgical facility. As of now, any of the surgical locations can offer the regenerative treatments on site.

Dr. Mike Yuan has been spearheading the procedures at American Spine.

The [platelet rich plasma] procedure is a very simple process. Draw blood, like a blood test, then centrifuge the blood, Yuan said, explaining that the centrifuge separates the components of the blood isolating the plasma that helps bodies heal.

Next, doctors inject the patients own plasma back into the problem area, focusing their healing functions directly on site.

Instead of waiting for your body to take it to the site, we are injecting there, Dr. Sandeep Sherlekar, a co-owner of American Spine, said.

This procedure uses the bodys natural method of healing in a more effective way, giving the body the green light to send more healing cells to help out.

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American Spine offers experimental fix for pain

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Toughest Breast Cancer May Have Met Its Match

Posted: December 9, 2014 at 7:56 am

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Tweet: Unresponsive triple-negative #breastcancer cells can be made susceptible to chemotherapeutic drugs.

Fast Facts: Only 20 percent of patients with so-called triple-negative breast cancer respond fully to chemotherapy. New research shows that chemotherapeutic drugs stimulate the HIF protein network in the cancer cells, enhancing their ability to survive. Giving HIF inhibitors together with traditional chemotherapy decreased tumor size in mice.

Newswise Triple-negative breast cancer is as bad as it sounds. The cells that form these tumors lack three proteins that would make the cancer respond to powerful, customized treatments. Instead, doctors are left with treating these patients with traditional chemotherapy drugs that only show long-term effectiveness in 20 percent of women with triple-negative breast cancer. Now, researchers at The Johns Hopkins University have discovered a way that breast cancer cells are able to resist the effects of chemotherapy and they have found a way to reverse that process.

A report of their findings was published online in the journal Proceedings of the National Academy of Sciences on Dec. 1.

Triple-negative breast cancers account for about 20 percent of all breast cancers in the United States, and 30 percent of all breast cancers in African-American women. In addition to being resistant to chemotherapy, they are known to include a high number of breast cancer stem cells, which are responsible for relapses and for producing the metastatic tumors that lead to the death of patients with cancer. Previous research revealed that triple-negative breast cancer cells show a marked increase in the activity of many genes known to be controlled by the protein hypoxia-inducible factor (HIF). Given these past results, a research team directed by Gregg Semenza, M.D., Ph.D., decided to test whether HIF inhibitors could improve the effectiveness of chemotherapy.

Our study showed that chemotherapy turns on HIF and that HIF enhances the survival of breast cancer stem cells, which are the cancer cells that must be killed to prevent relapse and metastasis, says Semenza, the C. Michael Armstrong Professor of Medicine at Johns Hopkins and a Johns Hopkins Kimmel Cancer Center expert. The good news is that we have drugs that block HIF from acting.

Semenzas study began by treating lab-grown triple-negative breast cancer cells with the chemotherapy drug paclitaxel and looking for changes in HIF levels. After four days of treatment, HIF protein and activity levels had increased, as had the percentage of breast cancer stem cells among the surviving cells. When Semenzas team, led by postdoctoral fellow Debangshu Samanta, Ph.D., genetically altered the cancer cells to have less HIF, the cancer stem cells were no longer protected from death by chemotherapy, demonstrating that HIF was required for the cancer stem cells to resist the toxic effects of paclitaxel, Semenza says.

At the molecular level, the team found that one of the ways HIF enhances the survival of the stem cells is by increasing the levels of a protein, multidrug resistance protein 1 (MDR1), which acts like a pump to expel chemotherapy from cancer cells. However, when triple-negative breast cancer cells were given paclitaxel plus the HIF inhibitor digoxin, MDR1 levels went down rather than up.

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Toughest Breast Cancer May Have Met Its Match

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Bid on Stem Cells and Alcohol-induced Tissue Injuries (R21 …

Posted: November 12, 2014 at 6:53 pm

Bid Date & Time: 09/07/15 5:00 PM Owner Solic Number: PA-12-232Status: biddingReport: 5964454 Country :United States State: MDCounty: Montgomery Location: Bethesda Scope: This Funding Opportunity Announcement (FOA) encourages applications to study human and non-human stem cells involved in alcohol-induced tissue injuries. Alcohol abuse is known to cause pathology in a number of organ systems. Disorders most commonly associated with chronic alcohol consumption include alcoholic liver disease (ALD), pancreatitis, cardiovascular disease, neural damage, endocrine dysfunction, osteoporosis, cancer, and immune dysfunction. The objective of this FOA is to understand the role of stem cells in alcohol-induced tissue damage and recovery, particularly how they are influenced by alcohol metabolism and their role in alcohol-related cancers. Notes: If you have difficulty accessing the full announcement electronically, please contact: NIH OER Webmaster FBOWebmaster@OD.NIH.GOV Plans: From Owner. See outside link. Outside Link: Owner Type: Public Buyer: National Institutes of Health (NIH) Address: 9000 Rockville Pike City: Bethesda State: MD Zip/Postal Code: 20892 Website: http://www.nih.gov Bid Pkg Source: National Institutes of Health (NIH) Address: 9000 Rockville Pike City: Bethesda State: MD Zip/Postal Code: 20892 Website: http://www.nih.gov

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Bid on Stem Cells and Alcohol-induced Tissue Injuries (R21 ...

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