Sunday, May 31, 2009

Transcriptional profiles of subsets within the CD34+ cell population in chronic phase CML

The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence by Ingmar Bruns and 16 co-authors, including Rainer Haas, Leukemia 2009(May); 23(5): 892-9 [Epub 2009(Jan 22)]. PubMed Abstract:
We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.

[Thanks to Alexey Bersenev].

Updates sent to Twitter, May 14-30

Updates about CSC sent to Twitter during May 24-30:

News item: Lung stem cells might cause cancer: Based on OA article [May 29]:
[PubMed Citation][Full text of the article is publicly accessible (via Gratis OA)].

Molecular signatures of prostate SC provide insights into prostate cancer (OA) [May 29]:
[PubMed Citation][Full text is publicly accessible (via Libre OA)].

Cancer stem cells in hepatocellular carcinoma: Recent progress and perspective [May 26]:

About inhibition of ABCG2-mediated multidrug resistance as a way to help to eradicate CSC (OA) [May 24]:
[PubMed Citation][Full text is publicly accessible (via Libre OA)].

Saturday, May 30, 2009

About updates hashtagged #cancerSC

On March 1, 2008, in a post entitled "An experiment with Twitter", I suggested that Twitter might be useful as an adjunct to this blog. The first set of "Updates sent to Twitter" was posted on March 7.

On May 8, 2009, I began adding the hashtag #cancerSC to updates micro-blogged on Twitter.

FriendFeed, described in a Wikipedia entry as a real-time feed aggregator, can be searched for this hashtag. As of today, the results of a search for #cancerSC yielded 15 items. Fourteen of the 15 items are ones that I have micro-blogged on Twitter. All of these 14 items have also been replicated in the weekly "Updates sent to Twitter" that have been posted to this blog.

A FriendFeed search provides a convenient way to review updates that have been hashtagged #cancerSC. Those who have joined FriendFeed can also post comments about individual updates. An advantage of FriendFeed is that, unlike Twitter, comments posted to FriendFeed need not be limited in length to 140 characters.

Short links to individual items can also be created on FriendFeed. These links permit individual items to be shared more widely. For example, the first update that was hashtagged #cancerSC (dated May 8, 2009) can be accessed via:

Sunday, May 24, 2009

Updates sent to Twitter, May 17-23

Updates about CSC sent to Twitter during May 17-23:

Migration rules: tumours are conglomerates of self-metastases [May 23]:
[PubMed Citation].

Interferon induces the terminal differentiation of glioma-initiating cells (GICs) [May 23]:

Pro-Cure and Adjuvantix to develop vaccine targeting cancer stem cells [May 23]:

About a Pten knockout mouse prostate cancer model (OA) [May 23]:
[Full text is publicly accessible (via Libre OA)].

Aldehyde Dehydrogenase 1 Is a Putative Marker for Cancer Stem Cells in Head and Neck Squamous Cancer [May 21]:
[PubMed Citation].

Thursday, May 21, 2009

Some recent Connotea bookmarks tagged "Cancer SC"

Cancer stem cells: a new paradigm for understanding tumor growth and progression and drug resistance, Rosaria Gangemi, Laura Paleari, Anna Maria Orengo, Alfredo Cesario, Leonardo Chessa, Silvano Ferrini, Patrizia Russo, Curr Med Chem 2009; 16(14): 1688-703 [PubMed Citation].

Targeting stem cells-clinical implications for cancer therapy, Lan C Tu, Greg Foltz, Edward Lin, Leroy Hood, Qiang Tian, Curr Stem Cell Res Ther 2009(May); 4(2): 147-53 [PubMed Citation].

TARGETING OF CANCER STEM CELL MARKER EpCAM BY BISPECIFIC ANTIBODY EpCAMxCD3 INHIBITS PANCREATIC CARCINOMA, Alexei V Salnikov and 9 co-authors, J Cell Mol Med 2009(Apr 2) [Epub ahead of print][PubMed Citation].

Number crunching in the cancer stem cell market, Malcolm R Alison, Shahriar Islam, Susan ML Lim, Breast Cancer Res 2009(Apr 24); 11(2): 302 [Epub ahead of print][PubMed Citation].

Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma, Dongho Choi, Hyo Won Lee, Kyung Yul Hur, Jae Joon Kim, Gyeong-Sin Park, Si-Hyong Jang, Young Soo Song, Ki-Seok Jang, and Seung Sam Paik, World J Gastroenterol 2009(May 14_; 15(18): 2258-64 [PubMed Citation][Full text via PMC].

Monday, May 18, 2009

CSC may be related to prognosis in primary breast cancer

Cancer Stem Cells May Be Related To Prognosis In Primary Breast Cancer, ScienceDaily, May 14, 2009. The first two paragraphs:
Breast cancer patients who received chemotherapy prior to surgery had heightened levels of cancer-initiating stem cells in their bone marrow, and the level of such cells correlated to a tumor's lymph node involvement, according to research from The University of Texas M. D. Anderson Cancer Center.
James Reuben, Ph.D., associate professor in the Department of Hematopathology, will present the findings in an oral presentation at the upcoming American Society of Clinical Oncology's annual meeting. It's the first prospective study to investigate the presence of breast cancer stem cells of primary breast cancer patients. The results suggest the need for additional biological therapies, as well as a potential and promising new direction for the study of micro-metastasis.

Updates sent to Twitter, May 10-16

Updates about CSC sent to Twitter during May 10-16:

Cancer stem cells - from initiation to elimination, how far have we reached? (Review) [May 13]:
[PubMed Citation][Full text PDF].

Origins and clinical implications of the brain tumor stem cell hypothesis, J Neurooncol 2009(May 9) [May 13]:
[PubMed Citation].

A new epigenetic cancer, Elie Dolgin, The Scientist, 11 May 2009 [May 13]:
[Full text is publicly accessible (free registration is required)].

CD133 may be specifically down-regulated during G0/G1? (PLoS ONE, May 10, 2009) [May 11]:
[Full text is publicly accessible (via Libre OA)].

Sunday, May 10, 2009

Updates sent to Twitter, May 3-9

Updates about CSC sent to Twitter during May 3-9:

Cancer stem cells in multiple myeloma, Nilanjan Ghosh, William Matsui, Cancer Lett 2009(May 8);277(1):1–7 [May 8][Author manuscript available in PMC May 8, 2009]:

Ontario Research Fund competition includes support for SC research [May 5]:

Malignant stem cells in childhood ALL: the debate continues! Blood 2009(Apr 30);113(18):4476-7; author reply 4477 [May 4]:
[PubMed Citation].

Malignant stem cells in childhood acute lymphoblastic leukemia: the stem cell concept revisited [May 4]:

Saturday, May 9, 2009

Leukemic stem cells in blast crisis CML

The CML stem cell: evolution of the progenitor by Scott A Stuart, Yosuke Minami and Jean YJ Wang, Cell Cycle 2009(May 1); 8(9): 1338-43 [Epub 2009 May 17][PubMed Citation][Full text PDF (Gratis OA)].

Last paragraph of the section of full text entitled CML Stem Cells and CML Therapy:
While the differences between CSCs and cells of the bulk tumor may prevent CSCs from being eliminated by therapies that target the bulk tumor, these differences may also provide unique therapeutic targets. Therefore, the identification of cancer stem cells may open the door to new targeted therapies as the differences between the cancer stem cell, the bulk tumor, and normal cells are realized. The observation that the leukemic GMPs in CML blast crisis largely depend on the β-catenin pathway for self-renewal point to this pathway as one attractive therapeutic target. Future studies with purified populations of HSCs and GMPs from patients with CML will be essential to identifying additional differences amenable to therapeutic intervention.
[CSCs = cancer stem cells; CML = chronic myeloid leukemia; HSCs = hematopoietic stem cells; GMPs = granulocyte-macrophage progenitors].

Found via Twitter. (Thanks to Alexey Bersenev).

Thursday, May 7, 2009

Clinical trial on the natural history of solid organ cancer stem cells (SOCSC)

Studying Stem Cells in Patients With Primary or Metastatic Solid Tumors. Identifier: NCT00892060
Study Type: Observational
Primary Objective:
To study and characterize, both quantitatively and qualitatively, solid organ cancer stem cells (SOCSC) from the time of tumor resection to the time of recurrence and/or metastasis using established phenotypic and functional markers of putative cancer stem cells from patients with primary or metastatic solid tumors.
Estimated Enrollment: 676
Study Start Date: February 2009
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Location: United States, Maryland
Principal Investigator:
Itzhak Avital, MD NCI - Surgery Branch
Found via Twitter (May 4, 2009).

Wednesday, May 6, 2009

Blog post about the complexity of CSC

Complexity of cancer stem cells by Alexey Bersenev, Hematopoiesis, May 6, 2009. [Twitter link to blog post] Final paragraph:
But not everything about CSC is so pessimistic. We know many good examples of successful targeting and eradication in tumors where the CSC model could be applied. We still have a lot of ways, other than surface molecules and signaling pathways, to target them. We are still developing a models to validate the concept. We can see clinical relevance and significance of CSC. Field is developing tremendously right now and a model is in the making.
… debating the existence of CSCs or their frequency is not a particularly useful exercise, and the scientific community would be well served to move beyond these issues. Rather, the more pertinent question is whether studying and targeting CSC is important for developing better forms of therapy. The answer to that query seems somewhat less clear.
Craig Jordan (U of Rochester)

Tuesday, May 5, 2009

Ontario Research Fund competition includes support for SC research

From the Programs & Funding page of the Ontario Ministry of Research and Innovation: Global Leadership Round in Genomics & Life Sciences (GL2) Competition Overview. Excerpts:
The Ontario Research Fund - Global Leadership Round in Genomics & Life Sciences (GL2) promotes research excellence in Ontario by supporting transformative, internationally significant research in genomics and gene-related areas of research. International collaboration is strongly encouraged for projects submitted to this competition.

The competition provides an opportunity for the province to fund truly transformative research and build on an area where Ontario researchers have demonstrated world-leading strength.

The Ontario Research Fund - Global Leadership Round in Genomics & Life Sciences competition focuses on scientific excellence and strategic value to Ontario, and targets leading-edge, large-scale research initiatives.

The minimum support provided by the GL2 to a project is $3.5 million.
What’s eligible for funding?

The Ministry encourages collaborative, transformational projects across institutions from the following areas:

* Genomics and Genomics-related research (human health, plants and animals)
* Stem cell research
* Proteomics research
When is the deadline for proposals?

The deadline for Notices of Intent is June 15, 2009.
The deadline for proposals is August 31, 2009.

Two recent videos about cancer stem cells

Two videos about CSC posted to YouTube on 2 May 2009 by the Cancer Institute of New Jersey:

1) Arnold J Levine and Robert A Weinberg discuss CSC (video: 37:53).

2) Cancer Stem Cells and Malignant Progression, Robert A Weinberg, Whitehead Institute, MIT (video: 1:04:06).

There are currently 31 of CancerInstNJ's videos on YouTube.

Monday, May 4, 2009

Updates sent to Twitter, April 26-May 2

Updates about CSC sent to Twitter during April 26-May 2:

The leukemic stem cell niche - current concepts and therapeutic opportunities. [May 1] See:
[PubMed Abstract]

Use of CTIP2 and BMI1 co-labeling to distinguish tumor initiating cells in human head and neck tumors (OA) [April 30]:
[Full text is openly accessible at PLoS ONE 2009(Apr 28); 4(4): e5367 (via Libre OA)].

PTEN, Stem Cells, and Cancer Stem Cells, Reginald Hill and Hong Wu, J Biol Chem 2009(May 1); 284(18): 11755-9 [April 29]:

Discussion of CSC at the recent Wisconsin Stem Cell Symposium in Madison [April 28]:

Cancer stem cells and their niche (review), Hiroko Iwasaki and Toshio Suda, Cancer Science (Mar 30, 2009) [April 27]:

Ability to continuously generate mammospheres in culture exhausted within five in vitro passages (OA) [April 26]:
[Full text is openly accessible at PLoS ONE 2009(Apr 24); 4(4): e5329 (via Libre OA)].