Inhibitory effects of omacetaxine on leukemic stem cells

Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice, by Yaoyu Chen and 5 co-authors, including Shaoguang Li, Leukemia 2009(Mar 26) [Epub ahead of print][PubMed Citation]. Examples of related news items:

Data suggesting that omacetaxine can eradicate leukemic stem cells may offer a breakthrough for CML, Physorg.com, March 26, 2009. Excerpt:

Data showing the ability of omacetaxine to kill leukemic stem cells in mouse models with drug-resistant chronic myelogenous leukemia (CML) are the subject of an advance online publication in the journal Leukemia, ChemGenex Pharmaceuticals Limited (ASX:CXS and NASDAQ:CXSP) announced today. The findings of this study provide new insights into the problem of minimal residual disease and may open the door to the development of a curative treatment strategy for some patients with CML. .....

Leukemic stem cell killer ‘omacetaxine’ help rises Chemgenex’s share, Stem Cell Research Blog, March 28, 2009. Excerpt:

ChemGenex Pharmaceuticals announced on March 26th, 2009 through online publication in the journal Leukemia, about the ability of omacetaxine to kill leukemic stem cells in mouse models with drug-resistant chronic myelogenous leukemia (CML). .....

On a shift in focus for CIRM

CIRM Close-Hauled, Seeks Bonds to Sustain Headway by Constance Holden, Science 2009(Mar 27); 323(5922): 1660-1 [PubMed Citation]. Excerpt:

A $210 million, 4-year program of "disease team grants," to be awarded this year, is the centerpiece of this thrust [toward support for translational research]. The program will entail perhaps 10 large grants to teams combining academic and industrial researchers working on a specific stem cell product for, say, Parkinson's disease. .....

Found via: Science Magazine on the State of CIRM, David Jensen, California Stem cell Report, March 27, 2009.

Updates sent to Twitter, March 22-28

Updates about CSC sent to Twitter during the fourth week of March:

Understanding the cancer stem cell hypothesis, Portal (OICR Newsletter) Winter 2009 [March 27]: http://tinyurl.com/ckcdab
[Full text is publicly accessible].

Stem-cell driven cancer: "Hands-off" regulation of cancer development [OA][March 26]: http://www.ncbi.nlm.nih.gov/pubmed/19279406
[Full text is openly accessible].

MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma [OA][March 26]: http://tinyurl.com/ccgt8y
[Full text is openly accessible].

Making Connections between Stem Cells and Cancer, NCI Director's Update, Mar. 24, 2009 [March 25]: http://www.cancer.gov/ncicancerbulletin/032409/page4
[Full text is publicly accessible].

Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits [March 25]: http://dx.doi.org/10.1038/nrc2620
[Full text is publicly accessible (free registration is required)].

Nuclear signalling by tumour-associated antigen EpCAM (reference 1 in Micromet news item [see below]) [March 24]: http://www.ncbi.nlm.nih.gov/pubmed/19136966

Micromet Has Started a New Phase 2 Trial with Adecatumumab in Colorectal Cancer Patients [March 24]: http://tinyurl.com/d9oc9j
[Full text is publicly accessible].

Oncolytic reovirus effectively targets breast cancer stem cells, Mol Ther 2009(Mar 17) [March 23]: http://www.ncbi.nlm.nih.gov/pubmed/19293772

Pancreatic cancer stem cells and relevance to cancer treatments, J Cell Biochem 2009(Mar 19) [March 23]: http://www.ncbi.nlm.nih.gov/pubmed/19301275

John Dick interviewed by Monya Baker

John Dick: careful assays for cancer stem cells by Monya Baker, Nature Reports Stem Cells 2009(Mar 26) [Full text is publicly accessible]. Excerpt:

What does the field need to move forward now?

It needs controversy.

The field of cancer stem cells needs controversy?

That's a little tongue in cheek. But it does. Controversy sparks better and better science. What it does is it actually eliminates sloppy thinking. There's been a real rush onto the cancer stem cell bandwagon in the last couple of years. People are talking about cancer stem cells here, there and everywhere, and in any old cell line. There was a huge slippage in the kind of criteria and rigor. People were using this terminology without any thought or any rigor based on some cell-surface marker or something like that. .....

[Thanks to Alexey Bersenev, via Twitter/cells_nnm].

Multipotent stromal cells as a Trojan horse?

Link between cancer stem cells and adult mesenchymal stromal cells: implications for cancer therapy by Christian Jorgensen, Regen Med 2009(Mar);4(2): 149-52 [PubMed Citation][Publicly accessible full text]. First paragraph:

A new concept has emerged in tumor biology suggesting that tumoral growth is derived from cancer stem cells (CSCs) present in the tumor. Moreover, these CSCs share common features with adult stem cells. In parallel, recent works have highlighted interactions between multipotent stromal cells (MSCs) and carcinoma, and the possible use of MSCs in cell-based anticancer therapies. Thus, translational research between fields of stem cells and tumor biology has changed our perception of carcinoma progression. The therapeutic implications are considerable and imply that to eradicate cancer we need to identify and target the CSCs as well as the MSCs that have migrated to the stroma.

Thanks to Alexey Bersenev, via Twitter/cells_nnm.

Updates sent to Twitter, March 15-21

Updates about CSC sent to Twitter during the third week of March:

Turning cancer stem cells inside-out: an exploration of glioma stem cell signaling pathways [March 20]: http://www.ncbi.nlm.nih.gov/pubmed/19286664 [Accepted manuscript version is publicly accessible].

Immune-Induced Epithelial to Mesenchymal Transition In vivo Generates Breast Cancer Stem Cells [March 20]: http://tinyurl.com/ckz6r7

HER-2, Notch, and Breast Cancer Stem Cells: Targeting an Axis of Evil, Clin Cancer Res 2009(Mar 15);15(6):1845-7 [March 19]: http://tinyurl.com/c3bvo9

Genomic instability en route to and from cancer stem cells: Cell Cycle 2009(Apr 11);8(7) [March 19]: http://www.ncbi.nlm.nih.gov/pubmed/19270518

Oncogenic Kras Initiates Leukemia in Hematopoietic Stem Cells, PLoS Biol 2009(Mar 17); 7(3): e1000059 [March 17]: http://tinyurl.com/ckp23s [Full text is openly accessible].

Treatment encourages more and more aggressive brain cancer stem cells [March 16]: http://www.nature.com/doifinder/10.1038/stemcells.2009.38 [Full text is publicly accessible].

Cancer stem cells and the cell cycle: targeting the drive behind breast cancer, Expert Rev Anticancer Ther, Mar09 [March 15]: http://tinyurl.com/bbwe33 [Full text is publicly accessible]

About the California-Canada relationship

San Diego's strong ties to Canada, by Sean Barr and Catriona Jamieson, SignOnSanDiego.com, Union-Tribune Publishing Co., March 19, 2009.

About: "San Diego's strong trade and biotech ties to Canada". Excerpts:

The California-Canada relationship makes sense on many levels. California and Canada have similar-sized populations and economies, and both economies are based on high-tech and innovation. Canada and California share $39 billion in bilateral trade, which supports more than 800,000 California jobs. California is Canada's second-largest market, and the total exports of goods from California to Canada are larger than those from Germany, the United Kingdom, France and Italy combined. ...

.....

The Canadian Consulate has helped foster these growing relationships. Hundreds of Canadian senior executives, research pioneers and government officials have come to San Diego to work with local business and research communities. The Canadian Consulate has organized a number of initiatives designed to facilitate bi-directional science and technology exchanges between San Diego and Canada. One of the newest and most comprehensive programs is the Canada-California Strategic Innovation Partnership, a program established to oversee and foster collaborations in areas ranging from health care to cancer stem cells to computer networks to environmental change. Last June at the BIO2008 International Convention in San Diego, Canada dedicated $110 million toward a Canada-California Strategic Partnership in Cancer Stem Cells. This collaboration brings together Canada's leading stem cell researchers with those from California, including Moores UCSD Cancer Center and the Burnham Institute.

CIRM Funding Priorities

Clinic vs. Basic Research: CIRM Funding Priorities, David Jensen, California Stem Cell Report, March 12, 2009. Excerpt:

Director Jeff Sheehy, a communications officer at UC San Francisco and a patient advocate representative, said the disease team project is already a year behind schedule. He said,

"We do not want to hamstring the disease team."

Requests for preliminary applications in that round have already gone out. It is scheduled to be awarded in September or October.

The goal set by the board of directors is just that. ...

Updates sent to Twitter, March 8-14

Updates about CSC sent to Twitter during the second week of March:

Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers [March 14]: http://tinyurl.com/cezflq

A radical bailout strategy for cancer stem cells, Cell Stem Cell 2009(Mar 6);4(3):196-7 [March 12]: http://www.ncbi.nlm.nih.gov/pubmed/19265655

Cancer stem cells and tumor response to therapy: current problems and future prospects [March 10]: http://www.ncbi.nlm.nih.gov/pubmed/19249647

In vivo imaging, tracking, and targeting of cancer stem cells. E Vlashi et al, JNCI (Mar 4) [March 8]: http://www.ncbi.nlm.nih.gov/pubmed/19244169

CIRM RFA 09-01 Disease Team Research Award Amendment

Copy of email from: CIRM RFA News (cirm_rfa_news@listserv.cahwnet.gov)
Received: March 11, 2009
Subject: CIRM RFA 09-01 Disease Team Research Award Amendment and FAQ

Colleagues:

For organizations interested in responding to RFA 09-01, CIRM Disease Team Research Awards, the following announcement is being forwarded to interested parties.

This email is to inform you that the Disease Team Research Award RFA 09-01 was amended and posted on 3/11/09. Specifically, Section III (Award Information) has been amended to clarify that $3 million to $20 million per project is the range for total funds requested (includes direct project costs, direct facilities costs, and indirect costs). The amended RFA 09-01 can be found at http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp <http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp> .

CIRM has prepared a Frequently Asked Questions (FAQ) document regarding the CIRM Loan Program for Disease Team Research Awards, RFA 09-01 (available at http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp <http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp>). We have tried to address your questions and concerns, but would appreciate it if you would contact Dr. Gil Sambrano if you have any additional questions. Dr. Sambrano can be reached at 415-396-9103 or by email at gsambrano@cirm.ca.gov <mailto:gsambrano@cirm.ca.gov>.

Video promoting CSC research

Video of Dr. Christopher Paige Interview on BNN, uploaded to PrincessMargaretHF on YouTube by the Princess Margaret Hospital Foundation on February 12, 2009 (to help to raise funds for research on cancer stem cells):

Dr. Chris Paige, Vice President of Research at University Health Network, talks to BNN viewers about what the discovery of cancer stem cells actually means for the researchers and scientists looking for new cancer treatments. Most chemotherapy treatments focus on cells that are regularly dividing, but cancer stem cells do not divide often. This understanding of cancer stem cells is leading to new ways of thinking about cancer treatment and new treatment targets.

The video has received 32 views as of March 11, 2008.

Updates sent to Twitter, March 1-7

Updates about CSC sent to Twitter during the first week of March:

Cancer stem cells in solid tumors: an overview, by O'Brien CA, Kreso A, Dick JE (Apr 2009) [March 7]: http://www.ncbi.nlm.nih.gov/pubmed/19249644

Brain tumors: New therapy surprisingly successful (March 06, 2009) [March 7]: http://tinyurl.com/c7exbm

Resistance to Endocrine Therapy: Are Breast Cancer Stem Cells the Culprits? [March 5]: http://www.ncbi.nlm.nih.gov/pubmed/19252972

Stem Cells Create Personalized Tumor in Mouse (about the niche dependency article by Katz, Skorecki & Tzukerman) [March 3]: http://tinyurl.com/czs52y

Variable niche dependency for the tumorigenic capacity of different cancer cell subpopulations [March 3]: http://www.ncbi.nlm.nih.gov/pubmed/19118034

First identification of cancer stem cells in Ewing's sarcoma family tumors (ESFT) [March 2]: http://www.ncbi.nlm.nih.gov/sites/entrez/19208848

Press release (24 Feb 2008) from Immunocellular Theraputics, about the CSC vaccine product candidate, ICT-121 [March 2]: http://tinyurl.com/demv6c

Cancer stem cells, hypoxia and metastasis, RP Hill et al. Semin Radiat Oncol 2009(Apr);19(2):106-11. Abstract [March 2]: http://tinyurl.com/dfxlop

Does eradication of CSC yield a successful therapeutic strategy? Question posed by RJ Jones & SA Armstrong [March 1] PMC: http://tinyurl.com/ccnnm6

[Page revised March 15, 2009]

Focal points for discussion about CSC

Cancer Stem Cells: Controversial or Just Misunderstood? Craig T Jordan, Cell Stem Cell 2009(Mar 6); 4(3): 203-5. Summary:

While a broad range of expertise has recently come to bear on the intriguing topic of cancer stem cells, the overall relevance of stem cells as they relate to cancer remains in dispute. In this commentary, underlying points of contention are described with the aim of defining focal points for discussion and future consideration.

Thanks to Alexey Bersenev: twitter.com/cells_nnm/status/1286475878

Cancer stem cells, hypoxia and metastasis

Cancer stem cells, hypoxia and metastasis, Richard P Hill, Delphine T Marie-Egyptienne, David W Hedley, Semin Radiat Oncol 2009(Apr);19(2):106-11. Abstract:

The successful growth of a metastasis, by definition, requires the presence of at least 1 cancer stem cell. Metastasis is a complex process, and an important contributor to this process is the influence of the tissue microenvironment, both cell-cell and cell-matrix interactions and the pathophysiologic conditions in tumors, such as hypoxia. A number of studies have suggested that normal stem cells may reside in “niches,” where cell-cell and cell-matrix interactions can provide critical signals to support and maintain the undifferentiated phenotype of the stem cells. In this article, the evidence that these niches may be hypoxic is described, and the potential role that hypoxia may play in maintaining the stem cell phenotype in cancers is discussed. Recent work has suggested that there may be a linkage between the stem cell phenotype and that induced by the process of epithelial-mesenchymal transition (EMT). EMT plays an important role in cell movement and organ formation during embryogenesis, and it is currently hypothesized to be a major mechanism by which epithelial cancers may generate cells that can form metastases. Recent evidence suggests that the expression of certain genes involved in EMT is influenced by low oxygen levels, again suggesting a linkage between stem cells and hypoxia. Whether this supposition is correct remains an open question that will only be answered by further experimentation, but the potential role of hypoxia is critical because of its widespread existence in tumors and its known role in resistance to both radiation and drug treatment.

An experiment with Twitter

An experiment by the Editor: I joined Twitter in late December, 2008 (see: Twitter / jimtill). Until now, I've seldom provided updates. However, as an experiment, I plan to post more frequently. The posts will be brief updates about topics of personal interest, including ones relevant to the two blogs that I currently edit (this one, and Be Openly Accessible or Be Obscure, a blog on topics related to the Open Access movement). The individual updates will involve no more than 140 characters (because that's the maximum allowed by Twitter), but related updates can be posted sequentially. My initial goal: to increase the number of "followers" of my Twitter page (and especially, to add "followers" who find the updates to be a useful adjunct to one or the other of the two blogs that I edit). The RSS feed url of updates to my Twitter page is: http://twitter.com/statuses/user_timeline/18376303.rss