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Labs Report 85 Percent Reduction in STR Analysis Time with SoftGenetics' ChimerMaker Software

By Uduak Grace Thomas

Users of ChimerMarker, a short tandem repeat chimerism analysis software solution marketed by SoftGenetics, are reporting a significant reduction in the time required to analyze STRs in blood samples of patients who have undergone bone marrow transplants.

The tool automates the process of assessing the chimerism ratio the proportion of donor cells relative to the host patients own cells in post-transplant cases based on the presence of STRs that are unique to both the patient and the donor, Don Kristt, head of molecular pathology at the Rabin Medical Center in Israel, explained to BioInform this week.

According to SoftGenetics, the software can be used to monitor chimerism levels in allogeneic and autologous stem cell transplants or hematopoietic stem cell transplants; bone marrow transplants; and cord and peripheral blood stem cell transplant samples.

SoftGenetics partnered with Kristt to develop the software, which it released last March (BI 3/18/2011). The company later added a module for testing fetal samples for maternal cell contamination prior to performing genetic testing for cystic fibrosis or other diseases (BI 9/2/2011).

The software provides capabilities for genotyping and chimerism analysis and tools to automatically identify donor and recipient peaks in samples following bone marrow transplants. It also calculates percent chimerism and quality metrics for single donor or double donor cases.

Dawn Wagenknecht, who supervises the HLA-Vascular Biology Laboratory at Franciscan St. Francis Health, told BioInform this week that her team was able to reduce the time required to calculate the ratio of donor to recipient cells in blood samples by as much as 85 percent.

She explained that the team ran parallel analyses of 10 blood samples using both ChimerMarker and a manual approach that the lab had used prior to purchasing the software, which involved manually sorting data generated by capillary sequencing in Excel spreadsheets, and then calculating the ratios either on the sheet or using a hand calculator.

In addition to the time savings, ChimerMarker also simplifies the analysis process because all the steps of the workflow are in a single package, she said.

The software also maintains records of the donor sample and the patients blood before transplantation so that the results from subsequent tests after transplant can be compared to the initial samples, she said.

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Labs Report 85 Percent Reduction in STR Analysis Time with SoftGenetics' ChimerMaker Software

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Age-Related Gene Expression Differences in Autism Detected in Post-Mortem Brain Samples

By Andrea Anderson

NEW YORK (GenomeWeb News) A study appearing online last night in PLoS Genetics has found gene expression differences in brain samples from children with autism spectrum disorder compared to adults with the condition, hinting that different pathological processes may be at work in the autistic brain depending on age.

A California research team used arrays to assess almost three-dozen post mortem brain samples from individuals with or without autism, gauging both gene expression and copy number alterations in a region called the prefrontal cortex. Along with comparisons between unaffected and affected individuals, the investigators looked at how expression patterns in samples from toddlers and children with ASD compared with those in samples from adolescents and adults with ASD.

Though some gene expression patterns in the prefrontal cortex turned up regardless of age in the ASD group, researchers also found age-dependent gene expression alterations in autism. For example, samples from children with ASD tended to show atypical expression of genes contributing to neuron number consistent with some of the unusual early brain growth patterns previously described in ASD whereas adult autism cases were marked by unusual expression profiles involving genes from signaling, immune, and repair pathways.

"We're showing that the adult condition where you have neuron loss and you have immunological activation isn't the way it began. It's an outcome," co-corresponding author Eric Courchesne, director of the National Institutes of Health-University of California at San Diego's Autism Center of Excellence, told GenomeWeb Daily News.

For more than a decade, studies have been finding distinct early brain development patterns in autism, including excess neurons in certain parts of the brain. This overgrowth seems to stop sometime during childhood, Courchesne noted. And by adolescence or adulthood, the enlarged brain regions seen in childhood generally seem to disappear through processes such as neuron loss and/or thinning in some cortical areas.

That has made it tricky to figure out the molecular roots of the early brain overgrowth seen by neuroimaging experiments or postmortem analyses, authors of the new study explained, though previous genetic studies have garnered clues about some of the age-independent processes contributing to autism.

"Up until now, there has been no information on the developmental, molecular pathology of autism that is, what's going wrong early in the brain that's responsible for excess and abnormal brain growth," Courchesne explained.

He and his colleagues used Illumina microarrays to assess expression profiles across the genome in post-mortem prefrontal cortex samples, comparing the patterns in unaffected and affected individuals and in younger and older individuals with ASD.

Because they were dealing with RNA from post-mortem brain samples, which are often not collected immediately after death, the researchers sent samples to Illumina for processing with its DASL assay to help get as much signal as possible out of the microarray experiments.

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New epilepsy gene located in dogs

Public release date: 23-Mar-2012 [ | E-mail | Share ]

Contact: Hannes Lohi hannes.lohi@helsinki.fi 358-919-25085 University of Helsinki

A new epilepsy gene for idiopathic epilepsy in Belgian Shepherds has been found in the canine chromosome 37. The research of Professor Hannes Lohi and his group conducted at the University of Helsinki and the Folkhlsan Research Center opens new avenues for the understanding of the genetic background of the most common canine epilepsies. The research also has an impact on the understanding of common epilepsies in humans. The research is published in the scientific journal PLoS ONE on March 23, 2012.

Epilepsy affects about 1-5% of the human population at some stage of live, and it includes a host of syndromes the age of onset, causes and prognosis of which vary significantly. Based on their basic mechanisms epilepsy syndromes are divided into genetic (idiopathic) epilepsies, structural / metabolic (symptomatic) epilepsies and epilepsies of unknown cause. Symptomatic causes refer to discernible external or structural change, whereas with idiopathic epilepsy there is a strong genetic background. A common denominator between the different syndromes are reoccurring epileptic seizures, which are divided according to an international classification into two main groups focal and generalized seizures based on clinical symptoms and research findings. About two thirds of the seizures in adults are focal in nature and one third generalized. In children and teenagers the occurrence of generalized forms of epilepsy is greater (ca. 50%).

Identification of the epilepsy gene on process

Genetic factors are estimated to play a role in the development of epilepsy in as many as 40% of epilepsy patients. Several genes affecting the development of symptomatic epilepsies have already been identified, but the genetic background of multifactorial idiopathic epilepsies often remain unknown. Both focal and generalized idiopathic epilepsies occur in Belgian Shepherds. The research group of Professor Hannes Lohi, working in collaboration with Danish, Swedish and American researchers in an EU-funded project, has made a major breakthrough by identifying a chromosome region associated with the most common form of epilepsy in dogs. By comparing the genome of dogs with epilepsy and healthy control dogs a gene region in chromosome 37 was discovered, which if homozygous, increases the risk of epilepsy seven-fold. In addition the research findings indicate that other, still unknown, genetic risk factors may be present in the breed.

The identified region has excellent neurological candidate genes for epilepsy and ongoing follow-up research is aimed to identify the specific gene causing epilepsy. Epilepsy genes have not previously been identified in this chromosome region, so the discovery will reveal an entirely new epilepsy gene in dogs and possibly also in humans. The type of epilepsy occurring in Belgian Shepherds is extremely common in also other breeds and thus the discovery may have an impact on the understanding of the epilepsies in different dog breeds.

"There are only few genes in the identified region and I believe that the ongoing analyses will help us to discover the specific epilepsy gene," says Professor Hannes Lohi who led the research. "This would give us a better understanding of the disease mechanisms and provide us with new diagnostic tools for the disease."

The Research group of Hannes Lohi has begun an extensive gene-sequencing project in which the entire identified chromosome region will be 'read through' with a next-generation sequencing method. By identifying the specific gene mutation an individual's epilepsy risk could be assessed, although the gene mutation may also be common in dogs that never become symptomatic of epilepsy.

Epilepsy is common among Belgian Shepherds

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Plerixafor Improves Acute Myeloid Leukemia Chemo Efficacy

Editor's Choice Academic Journal Main Category: Lymphoma / Leukemia / Myeloma Article Date: 23 Mar 2012 - 8:00 PDT

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The drug blocks these cells from binding to bone marrow by driving them into the bloodstream, where they are more susceptible to chemotherapy.

Geoffrey L. Uy, M.D., co-first author on the study and assistant professor of medicine, said:

52 individuals with acute myeloid leukemia (AML) whose AML was resistant to the standard chemotherapy regimen or who had relapsed, were enrolled to participate in the combined Phase I and II clinical trial. All 46 participants in the Phase II section of the trial received plerixafor. The researchers found that all 46 participants achieved complete remission (no evidence of cancer was found in the bone marrow or blood following treatment).

Uy, who treats patients at the Alivn J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, explained:

Results from earlier studies have demonstrated that mutations that cause AML may vary considerably among patients. Senior author, John F. DiPersio, M.D., Ph.D, the Virginia E. and Sam J. Golman Professor of Medicine, notes that all these leukemia cells, regardless of individual mutations, rely on the protective effects of the bone marrow.

DiPersio, who also treats people at the Siteman Cancer Center, said:

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Plerixafor Improves Acute Myeloid Leukemia Chemo Efficacy

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Potential Combination Therapy For Esophageal Cancer

Editor's Choice Academic Journal Main Category: Ear, Nose and Throat Also Included In: Cancer / Oncology Article Date: 23 Mar 2012 - 8:00 PDT

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In the March 20 issue of the journal Cancer Cell, researchers at The University of Texas MD Anderson Cancer Center reveal that the mTOR molecular pathway stimulates the activity of the Gli1 protein in the development and progression of esophageal cancer.

Senior author of the study, Mien-Chie Hung, Ph.D., vice president for basic research, professor and chair of MD Anderson's Department of Molecular and Cellular Oncology, explained:

Crosstalk between these two pathways is a challenge, but our experiments showed a combination of the mTOR inhibitor RAD-001 (Afinitor) and the Hedgehog inhibitor GDC-0449 (Erivedge) steeply reduced the tumor burden in a mouse model of esophageal adenocarcinoma."

The U.S. Food and Drug Administration (FDA) has approved both drugs for use in other types of cancer.

After examining 107 tissue samples of human esophageal cancer, the researchers found that 87 (81.3%) had a marker of Gli1 activated by Hedgehog and 80 (74.8%) had a marker of mTOR promotion of Gli1.

According to the researchers less than 20% of individuals suffering from esophageal cancer (one of the most aggressive forms of cancer) survive for 5 years. Furthermore, they highlight that since the 1980s, the disease has become more prevalent in the U.S by 5% to 10% each year. Obesity and inflammation are believed to contribute to this increased incidence.

In order to show how mTOR and Hedgehog, both involved in esophageal and other types of cancers, converge on Gli1, the team conducted experiments with cell lines, human tumor samples and mouse models.

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Potential Combination Therapy For Esophageal Cancer

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Identifying Acute Myeloid Leukemia Gene Mutations May Indicate Risk, Best Treatment

Newswise TAMPA, Fla. (March 23, 2012) An international group of researchers, including those from Moffitt Cancer Center in Tampa, Fla., have published a paper in the March 14 issue of the New England Journal of Medicine reviewing the results of a study that analyzed mutations in 18 genes of 398 patients who had acute myeloid leukemia (AML). They found that several mutated genes predicted improved outcomes when patients with certain gene mutations were given high-dose induction chemotherapy. Their findings suggest that mutational profiling could potentially be used for both risk stratification and also in helping health care providers make therapeutic decisions for some AML patients.

Previous studies have found that AML is a highly heterogenic disorder, said study co-author Hugo F. Fernandez, a senior member at Moffitt and associate chief of Moffitts Blood and Marrow Transplantation Division. Moreover, recent studies have revealed that a number of genetic mutations in AML patients might have prognostic value. The question of the presence of these gene mutations altering outcomes based on current therapy had not been answered to date.

Their paper cites a clinical trial carried out by the Eastern Cooperative Oncology Group (ECOG) in which dose-intensified chemotherapy improved outcomes in two age sets of AML patients. Based on these findings, the research team hypothesized that carrying out mutational analysis of all known molecular alterations occurring in more than 5 percent of patients with AML might allow for the identification of distinct, molecularly defined subgroups of patients who might benefit from dose-intensified chemotherapy.

The laboratory research team subsequently performed a mutational analysis on diagnostic samples from 398 patients enrolled in the ECOG clinical trial they cited and used patients frozen sample cells for extraction and profiling. The researchers validated the results of this latter group of 104 patients.

We found that intensification of the dose of anthracycline significantly improved outcomes and overall survival in patients with mutations in DNMT3A, NPM1 or MLL translocations, said Fernandez. This finding suggests that mutational profiling could be used to determine which AML patients will benefit from dose-intensive induction therapy.

Most importantly, said Fernandez, this study demonstrates how integrated mutational profiling of samples from a clinical trial cohort can advance understanding of the biologic characteristics of AML.

About Moffitt Cancer Center Follow Moffitt on Facebook: http://www.facebook.com/MoffittCancerCenter Follow Moffitt on Twitter: @MoffittNews Follow Moffitt on YouTube: MoffittNews

Located in Tampa, Moffitt Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center, which recognizes Moffitts excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt is also a member of the National Comprehensive Cancer Network, a prestigious alliance of the countrys leading cancer centers, and is listed in U.S. News & World Report as one of Americas Best Hospitals for cancer.

Media release by Florida Science Communications

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Identifying Acute Myeloid Leukemia Gene Mutations May Indicate Risk, Best Treatment

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Dr. Rebecca Carley : Vaccines

22-03-2012 12:29 Dr. Rebecca Carley talks about the vast dangers of vaccines and other AMA-approved treatments that actually do greater harm. website: drcarley.com (expand for more info) "The only safe vaccine is one that is never used." (Dr.James R. Shannon, former Director National Institute of Health) Vaccine Ingredients - Formaldehyde, Aspartame, Mercury + more The numbers of microbes, antibiotics, chemicals, heavy metals and animal byproducts is staggering. Would you knowingly inject these materials into your children? This following list of common vaccines and their ingredients should shock anyone --- eye-opening list here http://www.rense.com (page xcerpt) Acel-Immune DTaP - Diphtheria-Tetanus-Pertussis Wyeth-Ayerst 800.934.5556 * diphtheria and tetanus toxoids and acellular pertussis adsorbed, formaldehyde, aluminum hydroxide, aluminum phosphate, thimerosal, and polysorbate 80 (Tween-80) gelatin Act HIB Haemophilus - Influenza B Connaught Laboratories 800.822.2463 * Haemophilus influenza Type B, polyribosylribitol phosphate ammonium sulfate, formalin, and sucrose Attenuvax - Measles Merck & Co., Inc. 800-672-6372 * measles live virus neomycin sorbitol hydrolized gelatin, chick embryo Biavax - Rubella Merck & Co., Inc. 800-672-6372 * rubella live virus neomycin sorbitol hydrolized gelatin, human diploid cells from aborted fetal tissue BioThrax - Anthrax Adsorbed BioPort Corporation 517.327.1500 * nonencapsulated strain of Bacillus anthracis aluminum hydroxide, benzethonium chloride, and ...

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Study identifies genetic variants linked to fatty liver disease in obese children

Public release date: 23-Mar-2012 [ | E-mail | Share ]

Contact: Dawn Peters healthnews@wiley.com 781-388-8408 Wiley-Blackwell

New research found the genetic variant Patatin-like phospholipase domain containing protein-3 (PNPLA3) acting in conjunction with the glucokinase regulatory protein (GCKR) is associated with increased susceptibility to fatty liver disease in obese children. The study, published in the March issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, determined the PNPLA3 and GCKR single nucleotide polymorphisms (SNPs) were responsible for up to 39% of the hepatic fat content in this pediatric population.

Obesity is a global health concern and children are not unscathed by this epidemic. As a result, experts say nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in children and adolescents in industrialized countries. Previous studies indicate genetics significantly impacts the susceptibility of developing fatty liver and nonalcoholic steatohepatitis (NASH), particularly in early-onset disease, which places greater interest on childhood obesity.

For the current study, a team led by Dr. Nicola Santoro from Yale University School of Medicine in New Haven, Connecticut recruited 455 obese children and adolescents who underwent genotyping and fasting triglycerides and lipoprotein particles testing. Participants in this pediatric cohort had a mean age of 13 years with 181 Caucasian, 139 African American and 135 Hispanic children. Researchers measured hepatic fat content (HFF%) using magnetic resonance imaging (MRI) in a subset of 142 children.

Study findings show that rs1260326 in the GCKR gene is associated with higher triglycerides levels and higher levels of very-low-density lipoproteins (VLDL) in Caucasian and African American children. The GCKR SNP was associated with fatty liver in each of the three ethnic groups. A joint effect between PNPLA3 and GCKR SNPs was responsible for 32% of the HFF% in Caucasian, 39% in African American and 15% of Hispanic children. "Our findings confirm that obese youths with genetic variants in the GCKR and PNPLA3 genes may be more susceptible to fatty liver disease. We need to be cautious, though, and refrain to automatically extend this observation to the overall population. In fact, our data refer to a population of obese children and adolescents. I think that further studies involving lean subjects and adults may help to further define in more details these associations," said Dr. Santoro.

In a related editorial, Valerio Nobili with "Bambino Gesu" Children's Hospital and Research Institute in Italy concurs, "Dr. Santoro and colleagues determined the additive effect of PNPLA3 and GCKR variants explained over one third of hepatic fat content variance in obese children." He recommends that ethnicity data be replicated in larger study cohorts due to the small number of participants in each of the three groups.

The study authors suggest that the GCKR variant may lead to accumulation of fat in the liver through an increase in hepatic triglyceride production and further research is warranted to confirm their results. Dr. Santoro concludes, "While the small sample size raises the possibility of false negative results in our study, the presence of both GCKR and PNLPA3 genetic variants acting in combination confers susceptibility to fatty liver disease in obese children."

###

This study and editorial are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.

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Study identifies genetic variants linked to fatty liver disease in obese children

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Research and Markets: Progenitor and Stem Cell Technologies and Therapies Reviews the Range Of Progenitor and Stem …

DUBLIN--(BUSINESS WIRE)--

Dublin - Research and Markets (http://www.researchandmarkets.com/research/2fee68d4/progenitor_and_ste) has announced the addition of Woodhead Publishing Ltd's new book "Progenitor and Stem Cell Technologies and Therapies" to their offering.

Progenitor and stem cells have the ability to renew themselves and change into a variety of specialised types, making them ideal materials for therapy and regenerative medicine. "Progenitor and stem cell technologies and therapies" reviews the range of progenitor and stem cells available and their therapeutic application.

Part one reviews basic principles for the culture of stem cells before discussing technologies for particular cell types. These include human embryonic, induced pluripotent, amniotic and placental, cord and multipotent stem cells. Part two discusses wider issues such as intellectual property, regulation and commercialisation of stem cell technologies and therapies. The final part of the book considers the therapeutic use of stem and progenitor cells. Chapters review the use of adipose tissue-derived stem cells, umbilical cord blood (UCB) stem cells, bone marrow, auditory and oral cavity stem cells. Other chapters cover the use of stem cells in therapies in various clinical areas, including lung, cartilage, urologic, nerve and cardiac repair.

With its distinguished editor and international team of contributors, "Progenitor and stem cell technologies and therapies" is a standard reference for both those researching in cell and tissue biology and engineering as well as medical practitioners investigating the therapeutic use of this important technology.

Key Features:

- Reviews the range of progenitor and stem cells available and outlines their therapeutic application

- Examines the basic principles for the culture of stem cells before discussing technologies for particular cell types, including human embryonic, induced pluripotent, amniotic and placental, cord and multipotent stem cells

- Includes a discussion of wider issues such as intellectual property, regulation and commercialisation of stem cell technologies and therapies

For more information visit http://www.researchandmarkets.com/research/2fee68d4/progenitor_and_ste

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Research and Markets: Progenitor and Stem Cell Technologies and Therapies Reviews the Range Of Progenitor and Stem ...

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Stem Cell Therapy Used To Treat 9/11 Search And Rescue Dog

ANNAPOLIS, Md. (WJZ)One of the last search and rescue dogs from 9/11 lives here in Maryland. She was suffering from a painful condition until her owner took action with breakthrough technology.

Mary Bubala has the story.

Red is a search and rescue dog from Annapolis, but has traveled across the country. Her missions include Hurricane Katrina, the La Plata tornadoes and the Pentagon after 9/11.

They credit them with finding 70 percent of the human remains so that helped a whole lot of those families actually get closure, said Heather Roche, Reds owner.

Sept. 11 was Reds first search. Today shes one of the last 9/11 search and rescue dogs still alive.

She retired last summer due to severe arthritis.

It would be nice if her arthritis, if she felt better, that she could do those kinds of things that she misses, Reds owner said while fighting back tears. Alright I am going to cry.

Roche did some research and found an animal hospital in northern Virginia that uses breakthrough stem cell therapy to treat arthritis in dogs.

The Burke Animal Clinic is one of just a few across the country that use stem cell therapy.

The vet harvests 1 to 2 ounces of the dogs fatty tissue, activates the stem cells and then injects them back into the troubled areas.

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Stem Cell Therapy Used To Treat 9/11 Search And Rescue Dog

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Vet-Stem Announces StemInsure(R): A Small Fat Sample Now, a Lifetime of Stem Cells Later

POWAY, CA--(Marketwire -03/22/12)- Vet-Stem announced today the introduction of StemInsure. The StemInsure service provides banked stem cells that can be grown to supply a lifetime of stem cell therapy for dogs. One fat collection, in conjunction with another anesthetized procedure, gives access to a lifetime of stem cells.

Vet-Stem has trained over 3,500 veterinarians, provided stem cells for over 8,000 animals in the US and Canada and currently banks more than 25,000 doses for future therapeutic use. Many veterinarians and their clients have requested a method to collect and store stem cells when a dog is young, before it needs the regenerative cells for therapy. StemInsure was designed to meet this need.

A Vet-Stem credentialed veterinarian can collect as little as 5 grams of fat (about the size of a grape) from a dog or puppy during an anesthetized procedure. Many veterinarians and owners are electing to do this fat collection in conjunction with a spay or neuter. This small amount of fat is processed and stem cells are cryopreserved in Vet-Stem's state-of-the-art facility. The cells can be cultured in the future to provide enough stem cells to last for the lifetime of the dog. More information can be found at http://www.vet-stem.com/steminsure.php.

"Vet-Stem is pleased to provide StemInsure as a solution to the thousands of veterinarians and dog owners who recognize the value of Vet-Stem cell therapy. The ability to store the cells in conjunction with another procedure is a great way to ensure that the dog will have access to a lifetime of cell therapy while reducing the number of anesthetic events," said Dr. Bob Harman, DVM, MPVM, and CEO of Vet-Stem. Dr. Harman continued, "Currently, Vet-Stem Regenerative Cell Therapy is widely used to treat osteoarthritis, and tendon/ligament injuries. It is our expectation that the therapeutic use of adipose derived stem cells will continue to expand and add to the value of a lifetime supply of stem cells for dogs."

About Vet-Stem:In January of 2004, Vet-Stem introduced the first veterinary stem cell service in the United States. Since that time there has been rapid adoption of this technology for treatment of tendon, ligament, and joint injuries by the veterinary community. Studies have shown that mesenchymal stem cells can dramatically improve the healing of injuries and diseases that have had very few treatment options in the past.

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Vet-Stem Announces StemInsure(R): A Small Fat Sample Now, a Lifetime of Stem Cells Later

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Promising Data Presented On GenVec RSV Program

GAITHERSBURG, Md., March 23, 2012 /PRNewswire/ -- GenVec, Inc. (Nasdaq: GNVC - News) announced today that data were presented on GenVec's respiratory syncytial virus (RSV) vaccine program at the "Keystone Symposium on Viral Immunity and Host Gene Influence", which is taking place in Keystone, Colorado from March 21-26, 2012. The poster titled "Respiratory Syncytial Virus Neutralizing Antibodies Induced by Recombinant Adenovirus Vectors" #116 was presented on March 22, 2012 in Poster Session 1. The data were generated by the VRC and GenVec under a Cooperative Research and Development Agreement (CRADA). The presentation was given by Man Chen, PhD, Research Fellow, Viral Pathogenesis Laboratory, at the Vaccine Research Center (VRC) of the National Institutes of Health (NIH).

Data presented at the conference demonstrated encouraging preclinical proof-of-concept findings generated in non-human primates. Specifically, the data show GenVec's vaccine technology induced neutralizing antibody, and significant T-cell responses with a single administration. The immune responses were consistent with protective responses without disease potentiation and multiple administrations increased the neutralizing antibody responses.

"These data clearly demonstrate in a primate model that a vaccine utilizing our technology has significant potential to prevent RSV," stated Jason Gall, PhD, Senior Director of Research at GenVec and the company's lead RSV scientist. "These data support continued development of our pipeline of infectious disease vaccines based on our viral vector technology."

About Respiratory Syncytial Virus

RSV is the single most important viral cause of lower respiratory infections in infants and young children and there is no approved vaccine. According to the World Health Organization, nearly all U.S. children have been infected with RSV by two years of age. Although RSV infection usually produces cold-like symptoms, the infection can result in severe lower respiratory tract infection, which causes up to 130,000 pediatric hospitalizations per year in the U.S. RSV also causes repeated infections throughout life, placing the elderly and individuals with compromised cardiac, pulmonary, or immune systems at risk for severe disease. Among the institutionalized elderly, it is estimated there are about 15,000 deaths annually from RSV.

About GenVec

GenVec is a biopharmaceutical company using differentiated, proprietary technologies to create superior therapeutics and vaccines. A key component of our strategy is to develop and commercialize our product candidates through collaborations. GenVec is working with leading companies and organizations such as Novartis, Merial, and the U.S. Government to support a portfolio of product programs that address the prevention and treatment of a number of significant human and animal health concerns. GenVec's development programs address therapeutic areas such as hearing loss and balance disorders; as well as vaccines against infectious diseases including respiratory syncytial virus (RSV), herpes simplex virus (HSV), dengue fever, malaria, and human immunodeficiency virus (HIV). In the area of animal health we are developing vaccines against foot-and-mouth disease (FMD). Additional information about GenVec is available at http://www.genvec.com and in the Company's various filings with the Securities and Exchange Commission.

Statements herein relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding funding, grants, collaborations, revenues, cash burn rates, the development of products and the success of the Company's collaborations, including with Novartis and Merial, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. GenVec cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including the failure by GenVec to secure and maintain relationships with collaborators; risks relating to the early stage of GenVec's product candidates under development; uncertainties relating to research and development activities; risks relating to the commercialization, if any, of GenVec's proposed product candidates; dependence on the efforts of collaborators and third parties; dependence on intellectual property; currently unanticipated expenses, and risks that we may lack the financial resources and access to capital to fund our operations. Further information on the factors and risks that could affect GenVec's business, financial conditions and results of operations, are contained in GenVec's filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. These forward-looking statements speak only as of the date of this press release, and GenVec assumes no duty to update forward-looking statements.

Retail Investor and Media Contact:

GenVec, Inc.

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Promising Data Presented On GenVec RSV Program

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Spinal Cord Injury – James A., “Project Walk” Spinal Cord Injury Recovery” – Video

21-03-2012 15:41 Spinal cord injury treatment. http://www.projectwalk.org exists to provide an improved quality of life for people with spinal cord injuries through intense exercise-based recovery programs, education, support and encouragement.

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Spinal Cord Injury - James A., "Project Walk" Spinal Cord Injury Recovery" - Video

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Expert wants central bank for cord blood

A nodal public stem-cell bank in India is the need of the hour if blood cancer and thalassaemia patients are to benefit from stem-cell therapy, according to an expert.

We need an indigenous inventory of 30,000 units of umbilical cord-blood stem-cells, which would enable seven out of 10 patients seeking stem-cell transplant to find a ready match off the shelves, said P. Srinivasan, a pioneer in public cord-blood banking in the country, addressing members of the Ladies Study Group of the Indian Chamber of Commerce on Friday.

Cord blood, also called placental blood, is the blood remaining in the umbilical cord and placenta following childbirth after the cord is cut, and is routinely discarded with the placenta and umbilical cord as biological waste.

A rich source of stem cells, cord blood can be used to treat over 80 diseases, including certain cancers like leukaemia, breast cancer, blood disorders like thalassaemia major and autoimmune disorders like lupus, multiple sclerosis, Crohns Disease and rheumatoid arthritis.

Early clinical studies suggest these can even help avert corneal degeneration and restore vision in cases of blindness, help restore proper cardiac function to heart attack sufferers and improve movement in patients with spinal cord injury.

Since stem-cell matching is highly ethnicity dependent, the chances of an Indian finding a perfect match in a foreign country is a lot less compared to a resource pool of locally-donated units, the former resource person for WHO, now the chairman and managing trustee of Jeevan Blood Bank and Research Centre in Chennai, added.

Even if someone finds a match abroad, the cost of shipping the bag of matching cord blood could be as high as $40,000, as against the Rs 30,000 required for processing and storing one unit indigenously.

Srinivasan felt reaching the critical mass of 30,000 cord-blood units wasnt a big deal, given the fact that 20 million babies are born in India every year.

Purnima Dutta, the president of Ladies Study Group, agreed that raising awareness on the need to donate umbilical cord blood was the key.

As women and responsible citizens, the onus is on us to spread the word and encourage young couples to come forward and donate cord blood to ensure we can achieve this desired public-bank inventory which can save valuable lives, she said.

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Expert wants central bank for cord blood

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Stem Cell Transplant Program Offered at UVA Medical Center

What used to be medical trash is now treating cancer. The University of Virginia's Medical Center is the first place in Virginia to take advantage of stem cells from umbilical cords and they are pleased with the results.

Dr. Mary Laughlin, the director of stem cell transplantation at UVA,said, "These are cells that are routinely thrown away, these cells save lives."

A lab within the UVA Medical Center contains numerous tubes where non-embryonic stem cells reside. They come from umbilical cord blood and give hope topatients suffering leukemia, multiple myeloma and lymphoma.

Dr. Laughlin added, "They can completely replace a patient's bone marrow in the immune system. Oneof 10 cancer patients are able to find those cells through existing adult registries."

Thefive million babies that are born each year will soon solve that problem. The cells that are normally tossed out attack cancer cells.

Denise Mariconda, a nurse within the stem cell transplant program, stated, "It looks like a blood transfusion." Dr. Laughlin added, "It is in many ways like a cancer vaccine."

The first transplants were made in January and the transplant program at the UVA Medical Center admits it takes getting used to.

Mariconda said, "It is a process that's not like having your heart fixed in a one-day setting and you know that it's better."

These cells are not cause for controversy. Dr. Laughlin said, "Use of cord-blood is approved by all religious groups including the Vatican."

Babies' immune systems are not fully educated at the time of birth, making these cells effective. Dr. Laughlin, added, "That allows us to cross transplant barriers."

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Stem Cell Transplant Program Offered at UVA Medical Center

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Powerful new cells cloned: Key to immune system disease could lie inside the cheek

ScienceDaily (Mar. 21, 2012) Powerful new cells created by Cardiff scientists from cheek lining tissue could offer the answer to disorders of the immune system. While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from the School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases. Existing immune system research has focused on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

Dr Lindsay Davies, a member of the Cardiff team, said: "At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away. However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect -- bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth."

The findings have just been published online in Stem Cells and Development. The team has now been funded by the Medical Research Council to investigate the cloned cells further.

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Powerful new cells cloned: Key to immune system disease could lie inside the cheek

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Armenians can help save a life

Debbi Margosian Chapmans family hopes you will and is offering $10,000 to the person who is a bone marrow match for her to treat her leukemia. Because Debbi is Armenian, her doctors believe her best chances of finding a match is with the Armenian community.

Please join Dr. Frieda Jordan, president of the Armenian Bone Marrow Donor Registry (ABMDR), on Saturday, March 24, at 7 p.m., at the Armenian Cultural and Educational Center, 47 Nichols Avenue, Watertown, Massachusetts, for a presentation and bone marrow drive and become a hero for Debbi or the many other Armenians with blood cancers. If youre between 18-50 years old, you just need to give a quick swab of your cheeks so you can be entered into the Armenian Bone Marrow Donor Registry. If you are a match, in the majority of cases, your stem cells will be harvested in a manner similar to giving bloodthere is no anesthesia or surgery.

If you cant make it to the drive but want to be tested, please visit http://debbichapman.wordpress.com for more information.

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A new shortcut for stem cell programming

Public release date: 22-Mar-2012 [ | E-mail | Share ]

Contact: Dr. Frank Edenhofer f.edenhofer@uni-bonn.de 49-228-688-5529 University of Bonn

These stem cells can reproduce and be converted into various types of brain cells. To date, only reprogramming in brain cells that were already fully developed or which had only a limited ability to divide was possible. The new reprogramming method presented by the Bonn scientists and submitted for publication in July 2011 now enables derivation of brain stem cells that are still immature and able to undergo practically unlimited division to be extracted from conventional body cells. The results have now been published in the current edition of the prestigious journal Cell Stem Cell.

The Japanese stem cell researcher Professor Shinya Yamanaka and his team produced stem cells from the connective tissue cells of mice for the first time in 2006; these cells can differentiate into all types of body cells. These induced pluripotent stem cells (iPS cells) develop via reprogramming into a type of embryonic stage. This result made the scientific community sit up and take notice. If as many stem cells as desired can be produced from conventional body cells, this holds great potential for medical developments and drug research. "Now a team of scientists from the University of Bonn has proven a variant for this method in a mouse model," report Dr. Frank Edenhofer and his team at the Institute of Reconstructive Neurobiology (Director: Dr. Oliver Brstle) of the University of Bonn. Also involved were the epileptologists and the Institute of Human Genetics of the University of Bonn, led by Dr. Markus Nthen, who is also a member of the German Center for Neurodegenerative Diseases.

Edenhofer and his co-workers Marc Thier, Philipp Wrsdrfer and Yenal B. Lakes used connective tissue cells from mice as a starting material. Just as Yamanaka did, they initiated the conversion with a combination of four genes. "We however deliberately targeted the production of neural stem cells or brain stem cells, not pluripotent iPS multipurpose cells," says Edenhofer. These cells are known as somatic or adult stem cells, which can develop into the cells typical of the nervous system, neurons, oligodendrocytes and astrocytes.

The gene "Oct4" is the central control factor

The gene "Oct4" is a crucial control factor. "First, it prepares the connective tissue cell for reprogramming, later, however, Oct4 appears to prevent destabilized cells from becoming brain stem cells" reports the Bonn stem cell researcher. While this factor is switched on during reprogramming of iPS cells over a longer period of time, the Bonn researchers activate the factor with special techniques for only a few days. "If this molecular switch is toggled over a limited period of time, the brain stem cells, which we refer to as induced neural stem cells (iNS cells), can be reached directly," said Edenhofer. "Oct4 activates the process, destabilizes the cells and clears them for the direct reprogramming. However, we still need to analyze the exact mechanism of the cellular conversion."

The scientists at the University of Bonn have thus found a new way to reprogram cells, which is considerably faster and also safer in comparison to the iPS cells and embryonic stem cells. "Since we cut down on the reprogramming of the cells via the embryonic stage, our method is about two to three times faster than the method used to produce iPS cells," stresses Edenhofer. Thus the work involved and the costs are also much lower. In addition, the novel Bonn method is associated with a dramatically lower risk of tumors. As compared to other approaches, the Bonn scientists' method stands out due to the production of neural cells that can be multiplied to a nearly unlimited degree.

Low risk of tumor and unlimited self renewal

A low risk of tumor formation is important because in the distant future, neural cells will replace defective cells of the nervous system. A vision of the various international scientific teams is to eventually create adult stem cells for example from skin or hair root cells, differentiate these further for therapeutic purposes, and then implant them in damaged areas. "But that is still a long way off," says Edenhofer. However, the scientists have a rather urgent need today for a simple way to obtain brain stem cells from the patient to use them to study various neurodegenerative diseases and test drugs in a Petri dish. "Our work could form the basis for providing practically unlimited quantities of the patient's own cells." The current study was initially conducted on mice. "We are now extremely eager to see whether these results can also be applied to humans," says the Bonn scientist.

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A new shortcut for stem cell programming

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Somatic stem cells obtained from skin cells; pluripotency 'detour' skipped

ScienceDaily (Mar. 22, 2012) Breaking new ground, scientists at the Max Planck Institute for Molecular Biomedicine in Mnster, Germany, have succeeded in obtaining somatic stem cells from fully differentiated somatic cells. Stem cell researcher Hans Schler and his team took skin cells from mice and, using a unique combination of growth factors while ensuring appropriate culturing conditions, have managed to induce the cells' differentiation into neuronal somatic stem cells.

"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," explains Schler. "Thanks to this new approach, tissue regeneration is becoming a more streamlined -- and safer -- process."

Up until now, pluripotent stem cells were considered the 'be-all and end-all' of stem cell science. Historically, researchers have obtained these 'jack-of-all-trades' cells from fully differentiated somatic cells. Given the proper environmental cues, pluripotent stem cells are capable of differentiating into every type of cell in the body, but their pluripotency also holds certain disadvantages, which preclude their widespread application in medicine. According to Schler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ." Schler's somatic stem cells offer a way out of this dilemma: they are 'only' multipotent, which means that they cannot give rise to all cell types but merely to a select subset of them -- in this case, a type of cell found in neural tissue -- a property, which affords them an edge in terms of their therapeutic potential.

To allow them to interconvert somatic cells into somatic stem cells, the Max Planck researchers cleverly combined a number of different growth factors, proteins that guide cellular growth. "One factor in particular, called Brn4, which had never been used before in this type of research, turned out to be a genuine 'captain' who very quickly and efficiently took command of his ship -- the skin cell -- guiding it in the right direction so that it could be converted into a neuronal somatic stem cell," explains Schler. This interconversion turns out to be even more effective if the cells, stimulated by growth factors and exposed to just the right environmental conditions, divide more frequently. "Gradually, the cells lose their molecular memory that they were once skin cells," explains Schler. It seems that even after only a few cycles of cell division the newly produced neuronal somatic stem cells are practically indistinguishable from stem cells normally found in the tissue.

Schler's findings suggest that these cells hold great long-term medical potential: "The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made." So far, insights are based on experiments using murine skin cells; the next steps now are to perform the same experiments using actual human cells. In addition, it is imperative that the stem cells' long-term behaviour is thoroughly characterized to determine whether they retain their stability over long periods of time.

"Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Mnster Institute," says Schler. "We should realize that this is our chance to be instrumental in helping shape the future of medicine." At this point, the project is still in its initial, basic science stage although "through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects," emphasizes Schler. This, then, is the reason why a suitable infrastructure framework must be created now rather than later. "The blueprints for this framework are all prepped and ready to go -- all we need now are for the right political measures to be ratified to pave the way towards medical applicability."

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Somatic stem cells obtained from skin cells; pluripotency 'detour' skipped

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Somatic stem cells obtained from skin cells for first time ever

"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," explains Schler. "Thanks to this new approach, tissue regeneration is becoming a more streamlined - and safer - process."

Up until now, pluripotent stem cells were considered the 'be-all and end-all' of stem cell science. Historically, researchers have obtained these 'jack-of-all-trades' cells from fully differentiated somatic cells. Given the proper environmental cues, pluripotent stem cells are capable of differentiating into every type of cell in the body, but their pluripotency also holds certain disadvantages, which preclude their widespread application in medicine. According to Schler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ." Schler's somatic stem cells offer a way out of this dilemma: they are 'only' multipotent, which means that they cannot give rise to all cell types but merely to a select subset of them - in this case, a type of cell found in neural tissue - a property, which affords them an edge in terms of their therapeutic potential.

To allow them to interconvert somatic cells into somatic stem cells, the Max Planck researchers cleverly combined a number of different growth factors, proteins that guide cellular growth. "One factor in particular, called Brn4, which had never been used before in this type of research, turned out to be a genuine 'captain' who very quickly and efficiently took command of his ship - the skin cell - guiding it in the right direction so that it could be converted into a neuronal somatic stem cell," explains Schler. This interconversion turns out to be even more effective if the cells, stimulated by growth factors and exposed to just the right environmental conditions, divide more frequently. "Gradually, the cells lose their molecular memory that they were once skin cells," explains Schler. It seems that even after only a few cycles of cell division the newly produced neuronal somatic stem cells are practically indistinguishable from stem cells normally found in the tissue.

Schler's findings suggest that these cells hold great long-term medical potential: "The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made." So far, insights are based on experiments using murine skin cells; the next steps now are to perform the same experiments using actual human cells. In addition, it is imperative that the stem cells' long-term behaviour is thoroughly characterized to determine whether they retain their stability over long periods of time.

"Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Mnster Institute," says Schler. "We should realize that this is our chance to be instrumental in helping shape the future of medicine." At this point, the project is still in its initial, basic science stage although "through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects," emphasizes Schler. This, then, is the reason why a suitable infrastructure framework must be created now rather than later. "The blueprints for this framework are all prepped and ready to go - all we need now are for the right political measures to be ratified to pave the way towards medical applicability."

More information: Han D.W., Tapia N., Hermann A., Hemmer K., Hing S., Arazo-Bravo M.J., Zaehres H., Frank S., Moritz S., Greber B., Yang J.H., Lee H.T., Schwamborn J.C., Storch A., Schler H.R. (2012) Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors, Cell Stem Cell, CELL-STEM-CELL-D-11-00679R3

Provided by Max-Planck-Gesellschaft (news : web)

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Somatic stem cells obtained from skin cells for first time ever

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Stem Cell Therapy Used To Treat 9/11 Search And Rescue Dog

ANNAPOLIS, Md. (WJZ)One of the last search and rescue dogs from 9/11 lives here in Maryland. She was suffering from a painful condition until her owner took action with breakthrough technology.

Mary Bubala has the story.

Red is a search and rescue dog from Annapolis, but has traveled across the country. Her missions include Hurricane Katrina, the La Plata tornadoes and the Pentagon after 9/11.

They credit them with finding 70 percent of the human remains so that helped a whole lot of those families actually get closure, said Heather Roche, Reds owner.

Sept. 11 was Reds first search. Today shes one of the last 9/11 search and rescue dogs still alive.

She retired last summer due to severe arthritis.

It would be nice if her arthritis, if she felt better, that she could do those kinds of things that she misses, Reds owner said while fighting back tears. Alright I am going to cry.

Roche did some research and found an animal hospital in northern Virginia that uses breakthrough stem cell therapy to treat arthritis in dogs.

The Burke Animal Clinic is one of just a few across the country that use stem cell therapy.

The vet harvests 1 to 2 ounces of the dogs fatty tissue, activates the stem cells and then injects them back into the troubled areas.

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Stem Cell Therapy Used To Treat 9/11 Search And Rescue Dog

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Vet-Stem Announces StemInsure(R): A Small Fat Sample Now, a Lifetime of Stem Cells Later

POWAY, CA--(Marketwire -03/22/12)- Vet-Stem announced today the introduction of StemInsure. The StemInsure service provides banked stem cells that can be grown to supply a lifetime of stem cell therapy for dogs. One fat collection, in conjunction with another anesthetized procedure, gives access to a lifetime of stem cells.

Vet-Stem has trained over 3,500 veterinarians, provided stem cells for over 8,000 animals in the US and Canada and currently banks more than 25,000 doses for future therapeutic use. Many veterinarians and their clients have requested a method to collect and store stem cells when a dog is young, before it needs the regenerative cells for therapy. StemInsure was designed to meet this need.

A Vet-Stem credentialed veterinarian can collect as little as 5 grams of fat (about the size of a grape) from a dog or puppy during an anesthetized procedure. Many veterinarians and owners are electing to do this fat collection in conjunction with a spay or neuter. This small amount of fat is processed and stem cells are cryopreserved in Vet-Stem's state-of-the-art facility. The cells can be cultured in the future to provide enough stem cells to last for the lifetime of the dog. More information can be found at http://www.vet-stem.com/steminsure.php.

"Vet-Stem is pleased to provide StemInsure as a solution to the thousands of veterinarians and dog owners who recognize the value of Vet-Stem cell therapy. The ability to store the cells in conjunction with another procedure is a great way to ensure that the dog will have access to a lifetime of cell therapy while reducing the number of anesthetic events," said Dr. Bob Harman, DVM, MPVM, and CEO of Vet-Stem. Dr. Harman continued, "Currently, Vet-Stem Regenerative Cell Therapy is widely used to treat osteoarthritis, and tendon/ligament injuries. It is our expectation that the therapeutic use of adipose derived stem cells will continue to expand and add to the value of a lifetime supply of stem cells for dogs."

About Vet-Stem:In January of 2004, Vet-Stem introduced the first veterinary stem cell service in the United States. Since that time there has been rapid adoption of this technology for treatment of tendon, ligament, and joint injuries by the veterinary community. Studies have shown that mesenchymal stem cells can dramatically improve the healing of injuries and diseases that have had very few treatment options in the past.

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Vet-Stem Announces StemInsure(R): A Small Fat Sample Now, a Lifetime of Stem Cells Later

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Scientists identify new mechanism of prostate cancer cell metabolism

Public release date: 22-Mar-2012 [ | E-mail | Share ]

Contact: Jeremy Moore jeremy.moore@aacr.org 215-446-7109 American Association for Cancer Research

PHILADELPHIA Cancer cell metabolism may present a new target for therapy as scientists have uncovered a possible gene that leads to greater growth of prostate cancer cells.

Study results are published in Cancer Discovery, a journal of the American Association for Cancer Research.

Almut Schulze, Ph.D., a group leader in the Gene Expression Analysis Laboratory at Cancer Research U.K., and colleagues analyzed three metastatic prostate cancer cell lines and compared those findings with those of a nonmalignant prostate epithelial cell line.

"Cancer metabolism is a new and emerging target that can be exploited as a potential therapeutic, and our study identified one of the components for the growth of these cancer cells," she said.

The researchers analyzed the effects of gene silencing of 222 metabolic enzymes, transporters and regulators on the survival of the cell lines.

"This approach revealed a significant complexity in the metabolic requirements of prostate cancer cells and identified genes selectively required for their survival," said Schulze.

Researchers determined that the gene PFKFB4 was vital in many of these processes. Specifically, it was required to balance glycolytic activity and antioxidant production to maintain cellular redox balance in the cancer cells. When levels of this gene were depleted in laboratory models, tumor growth was inhibited. Higher levels of this gene were found in the metastatic prostate cancer cell lines.

Schulze concluded that this gene is required for tumor growth and thus could be manipulated with targeted therapies. Although this study was confined to prostate cancer, she believes the findings could be applicable in other cancers as well.

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Scientists identify new mechanism of prostate cancer cell metabolism

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Gene Expression Abnormalities in Autism Identified

Genetic studies find dysregulation in pathways that govern development of the prefrontal cortex in young patients with autism

Newswise A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms involved in abnormal early brain development and overgrowth that occurs in the disorder. The findings suggest novel genetic and molecular targets that could lead to discoveries of new prevention strategies and treatment for the disorder.

The study to be published on March 22 in PLoS Genetics uncovered differences in gene expression between brain tissue from young (2 to14 years old) and adult individuals with autism syndrome disorder, providing important clues why brain growth and development is abnormal in this disorder.

Courchesne first identified the link between early brain overgrowth and autism in a landmark study published by the Journal of the American Medical Association (JAMA) in 2003. Next, he tested the possibility that brain overgrowth might result from an abnormal excess of brain cells. In November 2011, his study, also published in JAMA, discovered a 67 percent excess of brain cells in a major region of the brain, the prefrontal cortex a part of the brain associated with social, communication and cognitive development.

Our next step was to see whether there might be abnormalities of genetic functioning in that same region that might give us insight into why there are too many cells and why that specific region does not develop normally in autism, said Courchesne.

In the new study, the researchers looked towards genes for answers, and showed that genetic mechanisms that normally regulate the number of cortical neurons are abnormal. The genes that control the number of brain cells did not have the normal functional expression, and the level of gene expression that governs the pattern of neural organization across the prefrontal cortex is turned down. There are abnormal numbers and patterns of brain cells, and subsequently the pattern is disturbed, Courchesne said. This probably leads to too many brain cells in some locations, such as prefrontal cortex, but perhaps too few in other regions of cortex as well.

In addition, the scientists discovered a turning down of the genetic mechanisms responsible for detecting DNA defects and correcting or removing affected cells during periods of rapid prenatal development.

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings in the brain at young ages have remained largely unknown. Until now, few studies have been able to investigate whole-genome gene expression and genotype variation in the brains of young patients with autism, especially in regions such as the prefrontal cortex that display the greatest growth abnormality.

Scientists including co-first authors Maggie Chow, PhD, and Tiziano Pramparo, PhD, at UC San Diego identified abnormal brain gene expression patterns using whole-genome analysis of mRNA levels and copy number variations from 33 autistic and control postmortem brain samples. They found evidence of dysregulation in the pathways that govern cell number, cortical patterning and cell differentiation in the young autistic prefrontal cortex. In contrast, in adult patients with autism, the study found that this area of the brain shows dysregulation of signaling and repair pathways.

Our results indicate that gene expression abnormalities change across the lifespan in autism, and that dysregulated processes in the developing brain of autistic patients differ from those detected at adult ages, said Courchesne. The dysregulated genetic pathways we found at young ages in autism may underlie the excess of neurons and early brain overgrowth associated with this disorder.

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Gene Expression Abnormalities in Autism Identified

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Ethics questions posed by 'precision medicine' are weighty, speaker tells HSU forum

What: Honors Forum on Faith and Intellect; topic is bioethics

When: Noon to 1 p.m. today

Where: Hardin-Simmons University, in the multipurpose room of the Johnson Building.

Keynote speaker: Dr. Peter Dysert II, chief of pathology, Baylor University Medical Center

Topic: "Precision Medicine: A Technology-driven Revolution"

Registration fees: $20 for conference and all meals ($10 for HSU employees and students); $5 each for keynote address and meal; no charge for presentations only.

Photo by Joy Lewis

Joy Lewis/Reporter-News Dr. James Denison, director of the Denison Forum on Truth and Culture, talks with guests before his keynote address, "Precision Medicine: Ethical Imperatives and Challenges" at Hardin-Simmons University on Thursday.

The day may come when some diseases are greatly diminished or even eliminated through genetic testing before people are even conceived that's the good news.

But what if that same testing can predict a child's future capabilities when conception occurs? Will that knowledge affect a couple's decision to have a child or even to marry?

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Ethics questions posed by 'precision medicine' are weighty, speaker tells HSU forum

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