On glioma recurrence and CSCs

Decreasing glioma recurrence through adjuvant cancer stem cell inhibition by Josh Neman and Rahul Jandial, Biologics: Targets & Therapy 2010(Jun 19); 4: 157-62 [OA review][FriendFeed entry]. Abstract:

Gliomas remain one of the most challenging solid organ tumors to treat and are marked clinically by invariable recurrence despite multimodal intervention (surgery, chemotherapy, radiation). This recurrence perhaps, is as a consequence of the failure to eradicate a tumor cell subpopulation, termed cancer stem cells. Isolating, characterizing, and understanding these tumor-initiating cells through cellular and molecular markers, along with genetic and epigenetic understanding will allow for selective targeting through therapeutic agents and holds promise for decreasing glioma recurrence.

An evolving concept of CSCs in tumor biology

An evolving concept of cancer stem cells in tumor biology: a lecture (34:38 min) by Jeremy N Rich. Webcast of the initial presentation at an Educational Session on Cancer Stem Cells and Treatment Resistance, AACR 101st Annual Meeting, April 17, 2010. [FriendFeed entry].

Comment: Dr. Rich's research has a primary emphasis on Glioma Cancer Stem Cell and Brain Tumors. An example of a recent publication: Integrin Alpha 6 Regulates Glioblastoma Stem Cells by Justin D Lathia and 10 co-authors, including Jeremy N Rich, Cell Stem Cell 2010(May 7); 6(5): 421-32. [PubMed citation][FriendFeed entry].

MicroRNA-34a is a potential therapeutic agent for glioma SC?

See the open-access article: microRNA-34a is tumor suppressive in brain tumors and glioma stem cells by Fadila Guessous and 7 co-authors, including Roger Abounader, Cell Cycle 2010(Mar 18); 9(6) [Epub ahead of print][FriendFeed entry][PubMed citation]. Last 3 sentences of the Abstract:

The new data show that miR-34a expression inhibits various malignancy endpoints in glioma stem cells. Importantly, they also show for the first time that miR-34a expression induces glioma stem cell differentiation. Altogether, the data suggest that miR-34a is a tumor suppressor and a potential potent therapeutic agent that acts by targeting multiple oncogenic pathways in brain tumors and by inducing the differentiation of cancer stem cells.

Targeting A20 Decreases Glioma SC Survival and Tumor Growth

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth by Anita B Hjelmeland and 10 co-authors, including Jeremy N Rich, PLoS Biol 2010(Feb 23); 8(2): e1000319 [FriendFeed entry][Connotea bookmark].

For a news release about this publication, see: Researchers identify a potential therapeutic target for brain cancer, EurekAlert, February 22, 2010. First paragraph:

Researchers at the Cleveland Clinic report the identification of a protein that is highly expressed in a subgroup of glioblastoma brain tumor cells and show that depletion of this protein increases the survival of mice with these tumors. This work will be published in the online open-access journal PLoS Biology.

CSC suppress immune response against brain tumor

Cancer stem cells suppress immune response against brain tumor, News Release, The University of Texas M. D. Anderson Cancer Center, January 15, 2010.

About two publications, one in Clin Cancer Res 2010(Jan 15);16(2):461-73 and the other in Mol Cancer Ther 2010(Jan);9(1):67-78.

See also: Cancer stem cells suppress immune response against brain tumor, Science Blog, January 15, 2010, and, Mechanism that helps brain cancer evade immune system attack discovered, Science News, January 16, 2010.

Featured Article in Cell Stem Cell (Nov 09)

Featured article in the November 6, 2009 issue of Cell Stem Cell (access to the Featured Article is free for all readers):

Malignant glioma remains challenging to treat, despite the use of aggressive surgery, radiotherapy, and chemotherapy. Although the concept of cancer stem cells reveals a new framework of cancer therapeutic strategies against malignant glioma, it remains unclear how glioma stem cells could be eradicated. In this issue, Miyazono and colleagues demonstrate that autocrine TGF-β signaling helps maintain glioma-initiating cells and find that chemical inhibition blocks the TGF-β-Sox4-Sox2 signaling axis, resulting in glioma cell differentiation in culture and loss of in vivo tumor-forming capacity. Therefore, clinical disruption of this pathway may represent a therapeutic paradigm against gliomas.

Autocrine TGF-β Signaling Maintains Tumorigenicity of Glioma-Initiating Cells through Sry-Related HMG-Box Factors by Hiroaki Ikushima and 5 co-authors, including Kohei Miyazono, Cell Stem Cell 2009(Nov 6); 5(5): 504-14). [Full text].

Mitogen independence of glioblastoma SCs

Proliferation of Human Glioblastoma Stem Cells Occurs Independently of Exogenous Mitogens by John J P Kelly and 11 co-authors, including Gregory Cairncross, Ian F Parney and Samuel Weiss, Stem Cells 2009(Aug 1); 27(8): 1722-33. [Epub 2009(Apr 23)][ResearchGATE Citation][PubMed Citation].

Hypoxic responses in glioma stem cells

Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells by Zhizhong Li and 11 co-authors, including Jeremy N Rich, Cancer Cell 2009(Jun 2); 15(6): 501-13 [FriendFeed entry] PubMed Abstract:

Glioblastomas are lethal cancers characterized by florid angiogenesis promoted in part by glioma stem cells (GSCs). Because hypoxia regulates angiogenesis, we examined hypoxic responses in GSCs. We now demonstrate that hypoxia-inducible factor HIF2alpha and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2alpha colocalizes with cancer stem cell markers. Targeting HIFs in GSCs inhibits self-renewal, proliferation, and survival in vitro, and attenuates tumor initiation potential of GSCs in vivo. Analysis of a molecular database reveals that HIF2A expression correlates with poor glioma patient survival. Our results demonstrate that GSCs differentially respond to hypoxia with distinct HIF induction patterns, and HIF2alpha might represent a promising target for antiglioblastoma therapies.

Comparing SC from the adult human brain and from brain tumors

A comparison between stem cells from the adult human brain and from brain tumors by Mercy Varghese and 8 co-authors, including Iver A Langmoen, Neurosurgery 2008(Dec); 63(6): 1022-34 [PubMed Citation].

Evaluation: Tali Siegal: Faculty of 1000 Medicine, 6 Jan 2009. Excerpt:

This study provides further evidence in support of the theory of human brain tumors deriving from apparent stem cell populations, rather than from transformation and differentiation of glial cells. The implication is that glioma stem cells should become the targets of future therapies, and, to that end, understanding the differences between normal and abnormally derived cells is important.