Category Archives: Translational Research

Will the Long History of Breast Cancer Research Culminate with Epigenetics Based Personalized Medicine?

Posted on July 13, 2012 by Nicole Kelesoglu

In the first century A.D, Roman family Greek slaves were surgeons. Celsus wrote an encyclopedic describing their methods in latin, laying a foundation for scientific literature on medical practice and surgery. The idea of diagnosis became paramount at this time, requiring close study and record keeping of injury and disease symptoms. It was understood that some breast cancers could be extirpated with breast removal. In the 19th century, after anesthesia and antisepsis had been established, (thank heavens!) a Johns Hopkins Hospital surgeon named William Stewart Halsted introduced, perhaps, the greatest advance to breast cancer treatment. The radical mastectomy. Throughout beast cancer history, the best prognosis post treatment, seemed to be based on early stage diagnosis. (1.) Today we have exceptional … Continue reading →

Posted in Biomarkers, Breast cancer, Clinical Studies, DNA Methylation, Genomewide Methylation Profiling, History & Trends, Microarray, Personalized Medicine, Transcriptome | Tagged , , , | 1 Comment

Dosage Makes All the Difference! Zahnow & Baylin Labs Show Epigenetic Reprogramming of Cancer

Posted on April 3, 2012 by Nicole Kelesoglu

Many of you are probably attending AACR this week. Cancer research into Epi-drugs is certainly a big theme. Along those lines, there is good news from the Cynthia Zahnow and Sephen Baylin teams at John Hopkins University in this paper, Hsing-Chen Tsai et al. Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effets on Hematological and Epithelial Tumor Cells.(March 2012) Cancer Cell 21, 430–446 . I’ll highlight the best bits. Obviously, the paper is awesome, and you need to read the details! The authors explain one of the most “striking effects” they observed is their accumulated evidence that this low dosage epigenetic chemotherapy can broadly reprogram stem-like cancer cells in solid cancers. Now, the exact molecular mechanisms of these … Continue reading →

Posted in Biomarkers, DNA Methylation, Flow Cytometry, Genomewide Methylation Profiling, Leukemia, Methylated DNA Capture, Oncology, Pharmacology / Toxicology, Stem Cells, Translational Research | Tagged , , , , , , , | Leave a comment

Further Evidence of the Importance of 5-hydroxymethylation in Cancer

Posted on March 20, 2012 by Nicole Kelesoglu

The discovery of the “6th base”, 5-hydroxymethylated cytosine, has resulted in rapid fire publication activity.  Researchers are exploring it’s part in demethylation dynamics, and its epigenetic function. Today I wanted to highlight the paper, H. Yang, et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation (March 2012) Oncogene 1-7. It provides further detailed analysis that is complementary to the work described by Hafner et al., please see my Q&A with Dr. Yegnasubramanian. The Oncogene paper research group, mainly out of Fudan University, looked at additional tissue types using an anti-5-hmC antibody for immunolocalization in paraffin embedded samples. They sampled human breast, prostate, liver, lung and pancreas, comparing them with corresponding matched normal surrounding tissues. … Continue reading →

Posted in Biomarkers, DNA Methylation, Diagnostics, History & Trends, Imaging, Immunohistochemistry, Oncology | Tagged , , , , | Leave a comment

The Epigenetic Two-Punch Cancer Treatment from Johns Hopkins

Posted on November 18, 2011 by Chris Womack

The big news in epigenetics this week is a two-drug epigenetic combo that shows results as good as the best FDA-approved chemotherapy in fighting non-small cell lung cancer, which accounts for about 80 percent such cancers. But missing from a lot of the mainstream accounts, the related study took a look at blood-based biomarkers, finding that they might serve as good indicators of whether a patient’s responding to treatment. Conducted by Johns Hopkins University’s Rosalind Juergens and colleagues, the phase I/II trial appears to be the most successful study of an epigenetic treatment of a solid tumor. I say this all the time, but keep in mind we’re still talking about a small sample size–the researchers studied 45 patients taking … Continue reading →

Posted in Applications, DNA Methylation, Diagnostics, Histone Modifications, Methyltransferases, Personalized Medicine, Translational Research | Tagged , , , , , | Leave a comment

Q&A with BLUEPRINT’s Henk Stunnenberg on the New Leukemia, Blood Epigenome Project

Posted on October 7, 2011 by Chris Womack

The European Union’s $53.5 million, 4-year BLUEPRINT project launched this week with the ambitious goal of cataloging the epigenomes of 100 different cell types, with a focus on hematopoietic cells and leukemia disease states. The project is only the second such effort associated with the International Human Epigenome Consortium—the first being the U.S. National Institutes of Health’s Roadmap Epigenomics Mapping Consortium—and it’s composed of 41 research entities, including university labs, research institutes, and drug and diagnostics companies. BLUEPRINT coordinator Henk Stunnenberg, a professor of molecular biology at the Radboud University Nijmegen in the Netherlands, says the project may publish early work as soon as a year from now, and that the epigenomes it uncovers have the potential to generate diagnostics … Continue reading →

Posted in Applications, Biomarkers, Chromatin Structure, DNA Methylation, Diagnostics, Gene Regulation, Histone Modifications, New Lab Methods, Next Gen Sequencing, Sodium Bisulfite Sequencing, Translational Research | Tagged , , , , , , , , | 1 Comment

Choose your Weapon! No Shortage of Trials for HDAC Inhibitor Drugs

Posted on September 30, 2011 by Nicole Kelesoglu

In India, Hindus call a three-pronged spear a trishul. The prongs symbolize nature, in its creative, preservative, and destructive states. Cancer research aims are akin to those natural states. Rapid cellular division is the creative state, for which chemotherapy and radiation, (or most recently synchronous chemoradiation), are used to kill the rapidly dividing cells. Angiogenesis meets a preservative requirement, bringing blood flow to tumors. Metastasis is a resulting destructive oncogenic state. Oncologist clinicians require an evolving therapy plan – a plan to wield like a specialized weapon to hit moving targets. Many clinical trials are now involving multiple drugs in synchronized or sequenced treatments. They hope to overcome obstacles like drug resistance…to promote synergistic drug actions…all to achieve improved patient … Continue reading →

Posted in Clinical Studies, Histone Modifications, Histones, History & Trends, Oncology, Pharmacology / Toxicology, Translational Research | Tagged , , | Leave a comment

Cellular Trash to Treasure – Exosomes

Posted on May 27, 2011 by Nicole Kelesoglu

Blood-Based Gene Expression Signatures in Non-Small Cell Lung Cancer.Clin Cancer Res. 2011 May 15 Thomas Zander, Andrea Hofmann, Andrea Staratschek-Jox, et al has been big in the international news recently. The authors are aiming to develop an RNA-stabilized blood test for asymptomatic lung cancer, using gene expression profiles, from what they believe to be immune effector blood cells – not cancer cells. The prognosis for lung cancer once you already have symptoms, is terrible. Their work is great news because this kind of non-invasive diagnostic test is desperately needed. However, there is another promising approach to transcriptome signature diagnostics to be aware of…Microvesicle shuttled RNA. Microvesicles, (MV), were once considered just cellular debris. We now know that blood, and many … Continue reading →

Posted in Applications, Biomarkers, Clinical Studies, Diagnostics, Flow Cytometry, Genetics, History & Trends, Next Gen Sequencing, Oncology, Pathology, Real-time PCR, Virology, microRNA, siRNA | Leave a comment

Epigenetics, Eh! to Promote Canadian Collaboration

Posted on April 30, 2011 by Nicole Kelesoglu

Late registration is still available online for Epigenetics Eh!, the Canadian Conference on Epigenetics, which is taking place in London, Ontario from May 4 to May 7th, 2011. Part of the stated mission for this conference is to promote a Canadian Epigenetics Research Network (EPIGENETICS CANADA). The epigenetic research areas of the speakers for this conference include, but are not limited to the following. Diabetes Early detection of cancer Leukemia Pluripotency in ES cells Proteomics to study protein import into the nucleus Genomic CNV and epigenetic changes in Neurobehavioral disorders Chromatin factors in brain development Molecular mechanisms underlying cell fate specification, proliferation, and differentiation of neural stem cells Genomic imprinting X chromosome inactivation Dicer expression and/or microRNA function. ING family … Continue reading →

Posted in Applications, Bioinformatics, Biomarkers, Cellular Biology, Chromatin Structure, DNA Methylation, Developmental Biology, Divergent Transcription, Evolutionary Epigenetics, Gene Regulation, Gene Silencing, Genetics, Hematology, Histone Modifications, Leukemia, Neuroscience, Non-coding RNA, Plant Epigenetics, Reproductive Biology, Stem Cells, Translational Research, chIP, siRNA | 2 Comments

Evaluating Multiple Biomarker Signatures – a Translational Science Endeavor

Posted on April 13, 2011 by Nicole Kelesoglu

Let’s chat about how important it is to consider epigenetics in the context of nature’s conversations – so to speak.  The systems biology research model assesses complex diseases by considering the interactions amongst multiple layers of dynamic biological processes.   When it comes to biomarkers for personalized medicine, the endgame will be defining values to the multiple types of profile signatures (i.e genomic, epigenomic, proteomic, etc) in the story.  Quite the project.  The trend here is to have collaboration conversations. If you are interested, please take time to read this brilliant review on blood based diagnostics, Emerging biomarkers-blood-based strategies to detect and monitor cancer. by Hanash, Baik & Kallioniemi.  Nature Reviews Clinical Oncology (March 2011).The authors suggest a causal model for … Continue reading →

Posted in Biomarkers, Diagnostics, History & Trends, Mass Spec, Oncology, Personalized Medicine, Translational Research, microRNA | Tagged , | Leave a comment

Get Rich Quick!

Posted on April 8, 2011 by Chris Womack

Well, not that kind of rich. It’s a new lab kit from New England Biolabs that lets researchers enrich samples with double-stranded methylated DNA, not grant dollars. The EpiMark Methylated DNA Enrichment Kit uses a macromolecule composed of the methyl-CpG binding domain of human MBD2 fused to the Fc tail of human IgG1, which is itself attached to paramagnetic protein A beads. According to an NEB-Sequenom press release, the technology was developed to study differentially methylated DNA. Looks like the protocol is mostly a few wash steps on a minimum of 4 ng DNA, a magnetic capture, and a 65° water incubation. Interestingly, NEB says each protein A can have as many as four MBD2 domains available to the solvent–each … Continue reading →

Posted in DNA Methylation, Diagnostics, New Lab Methods | Tagged , , | Leave a comment