cancer
Healthy Lifestyles: Good for You and Your Telomeres Too
We all know that a healthy lifestyle (diet high in whole foods and low in fat, moderate exercise, managing stress and good social support) is good for us. In fact I will go so far as to say that it isn’t even news that these things help our health and well-being. What is news, or at least newly published, is that these changes may also have a positive effect on telomerase activity and telomere length (1). Continue reading “Healthy Lifestyles: Good for You and Your Telomeres Too”
Site-specific copy number variations in cancer: A story begins to unfold
Tumor cells are characterized by many features: including uncontrolled proliferation, to loss of contact inhibition, acquired chromosomal instability and gene copy number changes among them. Some of those copy number changes are site-specific, but very little is known about the mechanisms or proteins involved in creating site-specific copy number changes. In a recently published Cell paper, Black and colleagues, propose a mechanism for site-specific copy number variations involving histone methylation proteins and replication complexes.
Previous work from Klang et al. had shown that local amplification of chromosomal regions occurs during S phase and that chromatin structure plays a critical role in this amplification (2), and other work by Black and colleagues (3) implicated KDM4A in changing timing of replication by altering chromatin accessibility in specific regions. Other research also had shown that KDM4A protein levels influence replication initiation and that KDM4A has a role in some DNA damage response pathways (4,5). Looking at the body of work, Black et al. hypothesized that KDM4A, with its roles in replication, might possibly provide link into the mechanism of site-specific copy number variation in cancer. Continue reading “Site-specific copy number variations in cancer: A story begins to unfold”
Priming an Effective T cell Response to Cancer
Cancer vaccines have been in progress for some time now. But a vaccine that is highly effective against cancer is not currently available.
However, an interesting report from Stanford University School of Medicine researchers, Dr. Irving Weissman, et al. shows some promise in a development of an altered means of stimulating the immune system, that could result in a stronger immune response and ultimately a better cancer vaccine. The paper by Weissman et al. was published electronically ahead of print in PNAS USA, May 20, 2013: “Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response.”
Continue reading “Priming an Effective T cell Response to Cancer”
Screening for Inhibitors of CD73 (5´-ectonucleotidase) Using a Metabolite Assay
CD73 also known as 5´-Ectonucleotidase (NT5E) is a membrane-anchored protein that acts at the outer surface of the cell to convert AMP to adenosine and free phosphate. CD73 activity is associated with immunosuppression and prometastatic effects, including angiogenesis. CD73 is highly expressed on the surfaces of many types of cancer cells and other immunosuppressive cells (1). A recent study by Quezada and colleagues showed that the high concentration of adenosine produced by the CD73-catalyzed reaction on glioblastoma multiforme cells, which are characterized by extreme chemoresistance, triggered adenosine signaling and in turn, the multi-drug resistance (MDR) phenotype of these cells (2).
Because of the roles of adenosine in immunosuppression, angiogenesis and MDR phenotypes, CD73 (NT5E) is an attractive therapeutic target. However, the current methods of assaying for the ectonucleotidase activity, HPLC and a malachite green assay, are cumbersome and not suited to high-throughput screening. The HPLC assay is expensive and difficult to automate and miniaturize (3). The malachite green assay is sensitive to phosphate found in media, buffers and other solutions used in the compound-screening environment.
To address the problem of developing a reliable high-throughput screening assay for CD73, Sachsenmeier and colleagues (3) looked to a luminescent ATP-detection reagent.
Continue reading “Screening for Inhibitors of CD73 (5´-ectonucleotidase) Using a Metabolite Assay”Cancer research yields unexpected results
Louis Pasteur once said “Chance favors the prepared mind”. Surely any scientist can attest to this. Discoveries of things like artificial sweeteners, Teflon, and penicillin were all unintended products of unrelated research. Recently, scientists at the Duke Cancer Institute studying the microevolution of enzymes involved in cancer happened upon a missing enzymatic link in a very unrelated area of research that has less to do with cancer than with the production of carpeting, apparel, and auto parts(1).
Nylon is a critical component in all of those products, any many, many more. Production nylon requires a compound called adipic acid. This intermediary, one of the most widely used chemicals in the world, is produced from fossil fuels and pollution released from its refinement process is a leading contributor to global warming. To date, there hasn’t been a “green” way of producing adipic acid because there is one critical enzyme in the synthesis pathway that isn’t available: 2-hydroxyadipate dehydrogenase.
Biochemical engineering on its own had not produced a sufficient dehydrogenase to do the job. Enter the cancer researchers. Cancer involves the microevolution of cells which offer benefits to the cells, sometimes including gain-of-function mutations in metabolic enzymes. Duke researchers identified a mutation in glioblastomas that alters the function of isocitrate dehydrogenase. The Duke team applied their knowledge of how enzymes change during cancer to lay the blueprints on a new method for producing clean, green, adipic acid. By using the same mutation framework, the scientist found that they could create enzymes from homoisocitrate dehydrogenase found in yeasts and bacteria that were capable of producing adipic acid from inexpensive sugars. The group still needs to scale up their production, a process that will still require a tremendous amount of work.
1. Reitman, Z. et al. (2012) Enzyme redesign guided by cancer-derived IDH1 mutations. Nat. Chem. Biol. Available online.
Does Your Daily Cup of Coffee Affect Your Risk of Cancer?
Is there an association between coffee consumption and incidence of cancer? The answer seems to depend on whom you ask, the study group involved, how much and what type of coffee the study participants drank and a host of other factors. Many research studies have found no link or only a weak link between the two, but recently a new study that showed a stronger association between coffee consumption and a lower risk of prostate cancer was published in the Journal of the National Cancer Institute (1). Why should we believe this new study when so many other studies have been unable to show a strong link?
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The Link Between Childhood Adversity and Cellular Aging
Adversity and stress are known risk factors for psychiatric disorders, cardiovascular and immune disease, cognitive decline and other health problems. The long-term negative effects of adversity seem to be greatest if the traumatic events were experienced during childhood, when the brain and other biological systems are developing and maturing. Researchers are working to identify the mechanisms involved and have identified telomere shortening as one possible mechanism by which adversity increases morbidity and mortality. Continue reading “The Link Between Childhood Adversity and Cellular Aging”
