Multidrug resistance and CSCs

Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities by Macus Tien Kuo, Antioxid Redox Signal 2009(Jan); 11(1): 99–134 [PubMed Citation]. Examples of sections of this review, accessible via the Author Manuscript in PMC:

IX. Redox Signaling in Multidrug-Resistant Cancer Stem Cells. Excerpt:

C. Signaling pathways in cancer stem cells

In addition to the efflux multidrug transporters, several crucial signaling pathways have been elucidated for cancer stem cell biology, including Wnt/β-catenin, Notch, sonic hedgehog, Bmi-1, the Hox family, and PTEN (161). Here, only the pathways that are most relevant to multidrug resistance are discussed.

X. Therapeutic Opportunities for Cancer Stem Cells. Final paragraph of this section:

Because cancer stem cells share many common features with those found in normal stem cells, caution must be exercised to avoid harming the normal stem cells (such as those in the bone marrow) during treatment. As better understanding of the role of cancer stem cells in the evolution of drug resistance is reached, one can expect that better treatment modalities targeting cancer stem cells also will be developed.

[The Author Manuscript in PMC is publicly accessible].

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.

Support for Warburg theory of cancer

Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer by Michael A Kiebish, Xianlin Han, Hua Cheng, Jeffrey H Chuang and Thomas N Seyfried, J Lipid Res 2008(Dec); 49(12): 2545-56 [Epub 2008 Aug 13][PubMed Citation]. News items:

Study results from Boston College, Department of Biology in the area of brain cancer cell biology published, Pharmacy Choice, December 29, 2008.

Don't Throw Off Warburg Theory of Cancer Just Yet, Medgadget, January 12, 2009. Excerpt:

Boston College biologists and colleagues at Washington University School of Medicine found new evidence to support Warburg's theory by examining mitochondrial lipids in a diverse group of mouse brain tumors, specifically a complex lipid known as cardiolipin (CL). They reported their findings in the December edition of the Journal of Lipid Research.

Characterization of human ESC with features of neoplastic progression

Characterization of human embryonic stem cells with features of neoplastic progression by Tamra E Werbowetski-Ogilvie and 15 co-authors, including Mickie Bhatia, Nat Biotechnol 2009(Jan 4) [Epub ahead of print][PubMed Citation]. Examples of news items about this research:

Scientists can now differentiate between healthy cells and cancer cells, Daily News, McMaster University, January 5, 2009.

Canadian researchers discover how to ID 'bad' from normal stem cells, CBC News, January 5, 2008.

Tests helps tease out 'good' stem cells from cancer-causing ones: study by Sheryl Ubelacker, The Canadian Press, 2009. The first two sentences:

One of the big worries about one day using stem cells to grow new organs and other tissues for curing disease is that these little regenerative powerhouses could give rise to tumours and end up doing more harm than good.

Now Canadian researchers have found a way to tell good stem cells from bad.

Minireview: PTEN, SC , and CSC

PTEN, stem cells, and cancer stem cells by Reginald Hill and Hong Wu, J Biol Chem 2008(Dec 30) [Epub ahead of print]. [Accepted Manuscript] PubMed Abstract:

Like normal stem cells, "cancer stem cells" (CSCs) have the capacity for indefinite proliferation and generation of new cancerous tissues through self-renewal and differentiation. Among the major intracellular signaling pathways, Wnt, Shh, and Notch are known to be important in regulating normal stem cell activities and their alterations are associated with tumorigenesis. It has become clear recently that phosphatase and tensin homologue (PTEN) is also critical for stem cell maintenance and that PTEN loss can cause the development of CSCs and ultimately tumorigenesis.

Autophagy and tumor dormancy in human ovarian cancer cells

The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells by Zhen Lu and 11 co-authors, including Robert C. Bast, Jr., J Clin Invest 2008(Dec 1); 118(12): 3917-29. [PubMed Citation]. The last sentence of the Abstract:

Thus, ARHI can induce autophagic cell death, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment.

A Commentary: Autophagy-induced tumor dormancy in ovarian cancer by Ravi K Amaravadi, J Clin Invest 2008(Dec 1); 118(12): 3837-40. PubMed Abstract:

Autophagy--a process of "self-eating" that involves enzymatic digestion and recycling of cellular constituents in response to stress--contributes to both cancer cell death and survival. In this issue of the JCI, Lu et al. report that controlled induction of tumor suppressor gene aplasia Ras homolog member I (ARHI) results in autophagic cell death of human ovarian cancer cells in vitro (see the related article beginning on page 3917). However, within xenograft tumors in mice, multiple factors within the tumor microenvironment switched ARHI-induced autophagy to a mechanism of tumor cell survival, leading to tumor dormancy. Since ARHI expression is suppressed in the majority of breast and ovarian cancers but is high in premalignant lesions, ARHI-induced autophagy could be manipulated for therapeutic benefit.

[The JCI publishes all research articles immediately in PubMed Central].

See also: Dormant Cancer Cells Rely on Cellular Self-Cannibalization to Survive, News Release, The University of Texas M. D. Anderson Cancer Center, December 31, 2008.

First CCSIP Call for Proposals

The Canada-California Strategic Innovation Partnership (CCSIP) has announced, in its News and Publications section, its first Call for Proposals (CFP) for Collaborative Initiatives Between California and Canada [16-page PDF], dated December 23, 2008. A Promotional Summary [3-page PDF] and FAQ Document [5-page PDF] are also available. The 16-page CFP is also available via the websites of ISTPCanada and the University of California Office of the President. An excerpt from the FAQ:

2. What types of proposals are requested under this CFP?

CCSIP is hosting a university-led Call for Proposals for Collaborative Initiatives between Canada and California. The objective of this CFP is to stimulate novel ideas, and catalyze the development of innovative multi–campus and multi–disciplinary research and educational collaborations between the two jurisdictions.

Under this CCSIP CFP, financial support is available for two types of bilateral initiatives, including the:

• Conduct of focused bilateral round tables, workshops and/or symposia that lead to novel methods or approaches for collaborative research. These proposals should request $15,000 to $50,000 in total funding².

[Footnote 2: Includes funds from both Canadian and Californian sponsors]

• Development and delivery of a detailed R&D business plans for early-stage bilateral initiatives that help to propel the concept to the next stage of development (following the conduct of workshops and associated research). These proposals should request about $100,000 in total funding.

Excerpts from the Promotional Summary:

Eligibility:

Each proposal must include a Principal Investigator (PI) from a participating Canadian university¹, and a PI from the University of California system.

[Footnote 1: A current list of participating Canadian universities may be found in Appendix A of the CFP document]

[Some paragraphs omitted, including a section on Type of Proposals Requested]

Focus of Proposals:

Bilateral university research teams are encouraged to put forward short proposals for collaborative initiatives that aim to address key priorities shared by California and Canada, capitalize on the complementary strengths of both jurisdictions and emphasize delivery to the market place.

[Some paragraphs omitted, including sections on Selection Criteria, Specifications for Letters of Intent and Complete Proposals, and Evaluation Process]

Deadlines:

• Letters of Intent: February 27, 2009; 2PM PST, UCOP and ISTPCanada will announce all selected Letters on March 16, 2009
• Requested Proposals: May 1, 2009, 2PM PST
• Funding Decisions: The CCSIP Steering Committee, together with UCOP and ISTPCanada, expect to announce funding for all successful bilateral initiatives by July 1, 2009

[Some additional paragraphs omitted, including sections on How to Apply and Additional Information]

Note that, in the Areas of Focus section of the CCSIP website, the first topic listed under Specific RD&D Project Areas is: Cancer Stem Cells.

A relevant previous post is: News release from CCISP, December 13, 2008.

Thanks to Cindy Bell for information about the first CCSIP Call for Proposals.