Erin Connelly

In a new study published in the January 17 edition of Cancer Cell, researchers have identified cells, known as pericytes, that play an important role in the prevention of cancer metastasis. Pericytes are a component of tissue vasculature and are necessary for angiogenesis, or blood vessel growth. Current antiangiogenic cancer therapies inhibit tumor growth by depleting pericytes and destroying the tumor’s blood supply.  However, this new study suggests that these therapies  may actually be contributing to more aggressive and metastatic cancers. In an interview with Decoded Science, the study’s senior investigator, Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Medicine at Harvard Medical School, said that this study ‘will lead to an immediate reevaluation of all cancer therapies targeting blood vessels’. Pericyte Study Overview Kalluri and colleagues from BIDMC and Hospital A. C. Camargo in the National Institute of Oncogenomics of Brazil depleted the number of pericyte cells in the breast cancer tumors of genetically-engineered mice. As expected, researchers saw a significant decrease in tumor size over a 25-day period. However, the researchers also found that the number of secondary lung tumors in the mice had increased threefold compared to the control mice, which indicates that [...]

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Cystic Fibrosis (CF) is a very common genetic disorder that currently has no cure and few effective treatments. The disease is caused by a defective recessive gene, which was identified in 1989. According to the Cystic Fibrosis Foundation, 1 in 31 Americans carry the CF gene, which is more common in Caucasians of European descent, but can appear in any race or nationality. The presentation of the disorder includes thick mucous, persistent lung infections, breathing difficulty, digestive disease, pancreatic insufficiency, and even the need for lung transplants in critical cases. Research into gene therapy as a treatment for CF has been ongoing for over two decades, but a breakthrough still remains elusive. However, in June 2011 the UK Cystic Fibrosis Gene Therapy Consortium, composed of scientists from Imperial College, London, University of Oxford and University of Edinburgh, received two Medical Futures Innovation Awards for their ‘Lentiviral Gene Therapy Programme for Cystic Fibrosis’, which holds great promise for effective long-term treatment of the disease. The Cystic Fibrosis Gene: The ΔF508 Mutation The majority of CF cases are caused by a mutation located in the mid-region of the long-arm of chromosome 7, which is known as the CFTR gene (cystic fibrosis transmembrane conductance regulator). The gene is essential for proper chloride ion transport and a mutation disrupts the [...]

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Can doctors prevent miscarriage after IVF through a minor change in clinical procedure? In vitro fertilization (IVF) is a process by which the egg and sperm of infertile couples are manually combined in a laboratory setting. If manual fertilization is successful, the embryos, typically about four or less, are placed inside the uterus for further development. This placement typically takes place within a few days of laboratory fertilization. However, IVF treatment using embryos that have been frozen and then thawed, instead of fresh embryos, is an increasingly widespread practice. This new practice has raised concerns about the viability of the frozen embryos and the effect of freezing on miscarriage rates. According to the American Pregnancy Association, the average success rate of IVF is already relatively low, with about a 30 to 35 percent success rate for women under 35 and a 6 to 10 percent success rate for women over 40. Thus, investigating and removing potential causes of pregnancy loss following IVF treatment is of great significance for the clinical community. New Research Analyzes Miscarriage Rate After IVF Treatment A new study, ‘Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages‘, was published in the [...]

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According to a study published on 3 January in Nature Communications, researchers at the University of Pittsburgh School of Medicine have improved the health and longevity of aging mice by injecting them with stem cell-like progenitor cells derived from the muscle of young mice. Within the body, stem/progenitor cells  have the ability to repair tissue. In aging tissue, these cells often show dysfunction in their ability to replicate, differentiate and repair damaged tissue. In an interview with Decoded Science, co-author Laura Niedernhofer, M.D., Ph.D, associate professor in Pitt’s Department of Microbiology and Molecular Genetics and the University of Pittsburgh Cancer Institute, said that ‘young stem cells were able to rejuvenate old stem cells in the laboratory’. These findings have the potential to have direct therapeutic benefit for the elderly, as well as patients with muscle-related disorders. Age Reversal: Using Young Stem Cells to Rejuvenate Aging Stem Cells The research team injected the stem/progenitor cells into the abdomens of 17-day-old progeria mice, which normally have a lifespan of 21 to 28 days. Progeria is a disease that causes abnormally quick aging, including loss of muscle mass, difficulty in mobility, muscle spasms and trembling. After receiving the injection of stem cells, results showed new blood vessel growth [...]

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Researchers at Georgetown University have developed a new method to grow normal cells and tumor cells from cancer patients in a laboratory setting, which previously had been impossible. Normal cells do not grow well in a laboratory and most cancer cells will not grow at all, which has been a significant barrier for research. In an interview with Decoded Science, the study’s senior investigator, Richard Schlegel, M.D., Ph.D., chairman of the department of pathology at Georgetown Lombardi Comprehensive Cancer Center, said that this new technique has the potential to have a major impact on diagnostics, pathology and the development of personalized, patient-specific cancer treatments. Growing Cancer Cells in the Lab The Georgetown research team, in collaboration with co-investigator Alison McBride, Ph.D. from the National Institutes of Health, discovered that the addition of Rho Kinase (ROCK) inhibitor and fibroblast feeder cells causes both normal and cancer cells to change into a state similar to that of stem cells. An important feature of stem cells is that they are able to continuously renew themselves for a long period of time. Many millions of cells may be generated in a short time from a small population of stem cells, even a single cell, [...]

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A key difference between linear and circular chromosomes is that linear chromosomes have ends. These ends are known as telomeres – a region of highly-conserved repetitive DNA sequence (usually TTAGGG). This repetitive DNA sequence signifies to the cellular machinery that the chromosome is not broken, which protects the end of the chromosome from aberrant repair attempts or fusion with other chromosome ends. Research on telomeres has been around since the 1930s; however, in 2009 Carol Greider, Elizabeth Blackburn and Jack Szostak were jointly awarded the Nobel Prize in Physiology or Medicine for their discovery of the enzyme telomerase and the protection of chromosome ends. This enzyme is thought to be responsible for the proliferation of a number of human cancers and is now the subject of a wide body of research. Key Components of Telomeres Telomeric DNA: As chromosomes divide during cell division, the ends are shortened and it is necessary for the cell to protect these gaps with telomeric DNA. Without the telomeric DNA, the ends of chromosomes would become shorter and shorter with every cell division until they ultimately became non-functional. The DNA flanking the telomeres is special because it is dominated by repeat sequences, which are not yet [...]

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Human genomes are made of double-stranded DNA arranged in the familiar double-helix formation. However, not all organisms have this arrangement for their genomes, specifically less complex organisms, whose genomes may be composed of single-stranded DNA or RNA. So with several genomic possibilities, why is double-stranded DNA such a good molecule to build a genome?  This is a fundamental chemical question about the stability of DNA. What is a Genome? A genome is the total amount of genetic material for an organism. The Human Genome Project, completed in 2003, was a worldwide endeavor to identify all of the genes in human DNA. Other objectives of the project were to sequence the 3 billion base pairs of human DNA, and store this information in databases for future analysis. The genomes of common lab organisms, such as yeast (Saccharomyces cerevisiae) and the fruit fly (Drosophila melanogaster) have also been sequenced. The human genome is composed of double-stranded DNA and approximately 20,000 genes. However, this is not the case for all organisms. Retroviruses, such as HIV, are composed of single-stranded RNA, while other viruses, such as the M13 bacteriophage, are composed of single-stranded DNA. The Structure of DNA In general, human DNA is made of [...]

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Gregor Mendel was a nineteenth century monk who demonstrated the basic principles of genetic inheritance via his experiments with pea plants. The significance of Mendel’s work was not recognized until the twentieth century, when several scientists reproduced Mendel’s original experiments. He is now considered to be the founder of modern genetics. The following is a simple experiment to extract, or precipitate, DNA, which is the carrier of genetic information. DNA is tightly coiled inside the nucleus of a cell, and is protected by proteins and the cellular membrane. Using common household reagents, the following steps will remove those barriers and make DNA visible to the naked eye. Step 1: Make a Pea Solution Combine 250 ml (~1 cup) of peas with 1.5 ml (~1/4 teaspoon) common table salt and 500ml (~2 cups) of cold water in a blender, or by using a mortar and pestle. It is essential that the water be cold (ice water is preferable) as the low temperature slows down cellular reactions and will increase the amount of DNA yielded at the end of the experiment. Step 2:  Add Detergent Strain the pea mixture to remove all solids from the solution, and then add 60 ml (~4 tablespoons) [...]

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Gel electrophoresis is an experimental procedure that uses an electric current to separate mixed proteins or nucleic acids based on their differing sizes, charges or structures. The procedure is used extensively in laboratory research in disciplines concerned with detecting DNA or analyzing microscopic particles, such as genetics, biochemistry, immunology and molecular biology. Gel electrophoresis is also a crucial first step in the protocol for other analytical procedures like Western Blotting (separation of proteins), Southern Blotting (DNA detection) and Northern Blotting (RNA detection). How Gel Electrophoresis Works Gel electrophoresis uses an electric current passed through a gel medium to separate the nucleic acids or proteins in a sample. As the sample migrates in the gel in response to the electric current, the small particles move more easily and more quickly than the larger particles, which results in a distinct banded pattern in the gel. This banded pattern is visualized via the application of staining agents, such as ethidium bromide, which reveals the gel bands under UV light, or silver stain, which is typically used to detect proteins.  The silver stain is compatible with mass spectrometry techniques for further analysis of the protein composition. Materials and Methods: Gels The type of gel, percent concentration, and experimental [...]

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Geldanamycin and its derivatives (17-AAG, 17-DMAG) are part of the benzoquinone ansamycin family, a class of molecules which demonstrate marked antimicrobal activity against bacteria, parasites and some viruses. These antibiotics are naturally produced by microorganisms as a defense mechanism against disease-causing invaders. Geldanamycin was first isolated in Streptomyces hygroscopicus, a filamentous soil bacterium,  in 1970 and was later identified to have strong anti-tumor qualities. Since the 1990s, research into the anti-cancer properties of geldanamycin has been ongoing. Current studies continue to reveal promising insights into the mechanism of the drug and its potential for use in a clinical setting. Geldanamycin Mechanism The Met Receptor It has been shown, through research done by Vande Woude, Xie, Webb, Panaretou and others, that the met receptor is very influential in the metastasis and invasion of cancer cells.  Met is normally expressed as a membrane receptor in epithelial cells where human growth factor (HGF) binds and causes signaling. This met/HGF signaling is important for a number of bodily processes, including wound healing, embryo development, and tissue repair. However, when the met receptor is abnormally expressed, it triggers dysfunctional cellular signaling. This can lead to the development of tumors, cell invasion, and metastasis. Abnormal met signaling [...]

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