Monday, April 30, 2012
Activation of silenced tumor suppressor genes in prostate cancer cells by a novel energy restriction-mimetic agent.
In this manuscript published in The Prostate, Ching-Shih Chen's group from Ohio State show that energy restriction (either by novel mimetics or 2-deoxyglucose), led to down-regulation of DNMT1 and 3A (DNA methyltransferases 1 and 3A) and subsequent reactivation of previously hypermethylated tumor suppressor genes - caloric restriction has been shown to suppress cancer in animal models, but these findings provide a novel mechanism for the effect -- read it for yourself at http://onlinelibrary.wiley.com/doi/10.1002/pros.22530/pdf
Friday, April 27, 2012
Just what we've been waiting for: Quantitative Sequencing of 5-Methyl-cytosine and 5-Hydroxymethylcytosine at Single-Base Resolution
In this paper published yesterday in Science Express by Wolf Reik and Shankar Balasubramanian and friends, a novel method to quantitate hydroxymethylcytosine is described -- as anyone who has tried to quantitate this "new" base knows, it is not so easy -- but this technique takes advantage of the specific oxidation of 5hmC to 5fC, using a readily available chemical, potassium perruthenate. This is followed by bisulfite conversion, which differentially converts 5hmC, leaving 5mC unconverted (typically both 5hmC and 5mC are protected during bisulfite conversion). The sequence resulting from this oxBS is compared to a regularBS (bisulfite conversion), allowing quantification of 5hmC content. Why do we care? Well it has already been shown that 5hmC regulates cell lineage determination in mouse stem cells -- we work on cancer, but it doesn't take a rocket scientist to figure out that there are similarities between cancer cells and stem cells -- now we have an "easy" tool to look at this within particular genes -- Note to my Lab: I have just ordered potassium perruthenate....please read this paper! Here's the link to the manuscript -- you may need to have access to Science magazine --click here--
Thursday, April 26, 2012
In this paper from down-under, the novel finding that Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import, and able to inhibit replication of HIV-1 and dengue virus -- ivermectin -- yep, that is the stuff that we give our dogs every month to prevent heartworm...although all the experiments here are in vitro and at high drug concentrations, these findings are interesting because they could provide the basis for future drug design as well drug target(s) -- the manuscript is open access - read all about it here -- by Wagstaff et al.
Wednesday, April 25, 2012
It has long been known that tumor DNA is hypomethylated compared to DNA from normal tissue - one measure often used as a surrogate for global DNA methylation is that of LINE-1 retrotransposons, so-called "junk DNA" that makes up approximately 20% of the human genome -- there are about 500,000 of these elements in our genome - and 80-100 of these are capable of becoming activated -- an event that can cause major disruption to the nucleus -- the cell prevents this from occurring by heavily methylating these elements to suppress transcription -- but why do they become activated in cancer? and as this paper suggests, is it possible that they can act to repair damaged telomeres? And, if so, does that mean that we should be inhibiting LINE-1 rt as a cancer therapy? How could we prevent LINE-1 activation in the first place...PNAS has a free on-line series of papers on retrotransposons and telomerase, just click here--
Wednesday, April 18, 2012
this website compiles data resulting from the treatment of cancer cell lines with common chemotherapeutics, giving insight as to what genes might be good as targets for various cancers -- apparently the data is already changing the way we look at treating diseases such as Ewing's sarcoma -- again this is data that is available for everyone, the experiments are already done - that's my kind of data... you can get to the home page of the site here -- Genomics of Drug Sensitivity in Cancer
Wednesday, April 11, 2012
this is not usually my topic, but if the findings discussed in this recent Science paper are able to be replicated in humans, the impact will be huge! An old drug, Bexarotene, was able to not only "dissolve" the Beta-amyloid deposits in a mouse model of Alzheimer's by 50% in a few days, but reversed cognitive defects as well -- sounds almost too good to be true! Hopefully this drug will work the same way in humans, but just like cancer, mouse models don't always react to drugs in the same ways as humans...if you want to read about it, check out the journal article here --
Monday, April 2, 2012
As far as I recall, we've always needed an RFA or a PA for these type of grants from the NCI - so this is good news! Click here for the specifics...R21 and R03
We just love free data portals! Someone else has already done the technical stuff, and you just need to figure out what it means - and that's usually the most fun part of science...anyhow, thanks to the Broad Institute, and funded by Novartis, there are currently mutation data for 1651 genes across 909 cell lines (and growing) available free of charge...they do ask that you register, however it is free for research and instantaneous -- just click here!
Today my grad student Katy asked me what "soft money" meant -- I found this article that really describes not only what soft money (money from grants) is, but how most faculty in the health sciences rely on it and how it has affected administrative decisions at universities...the article is mostly discussing Emory University, but the ideas apply across the board...the article is by Donald G Stein, and you can read about it by clicking here...