Aging, inflammation and cancer

Aging and inflammation: etiological culprits of cancer by Aamir Ahmad and 5 co-authors, including Fazlul H Sarkar, Curr Aging Sci 2009(Dec); 2(3): 174-86 [PubMed Citation][Full text in PMC]. Excerpt from the full text:

In the context of cancer, like normal tissues, various cancerous tissues also harbor a minor population of cells with enormous self-renewal and tumor-initiating capacity. Such cells are referred to as tumor-initiating cells or cancer stem cells, which offer an attractive target for cancer therapy [136] provided that normal stem cells are spared from the side effects of therapy. A number of molecular events that mark stem cell aging also occur in tumors in the elderly [134] and, as such, play important roles in the processes of cancer and aging, suggesting that these two processes are intertwined.

Comment: The full text of this article is available via PubMed Central (PMC). However, if accessed at the website of Current Aging Science (a journal of Bentham Science Publishers), the full text can only be purchased, and prior registration is required.For some background information about this publisher, see an entry in the French version of Wikipedia [Google translation into English]. (This entry is currently not available in the English version of Wikipedia).

CSC news roundup 2009-12-24

• An adult tissue-specific stem cell molecular phenotype is activated in epithelial cancer stem cells and correlated to patient outcome by Thomas Hussenet and 4 co-authors, including Stanislas du Manoir, Cell Cycle 2010(Jan 23); 9(2) [Epub ahead of print][PubMed Citation][Connotea bookmark].


• Differential Destruction of Stem Cells: Implications for Targeted Cancer Stem Cell Therapy by Mary E Sehl and 3 co-authors, including Kenneth L Lange, Cancer Res 2009(Dec 15); 69(24): 9481-9 [PubMed Citation][Connotea bookmark][ResearchGATE entry].


• EZH2 Is Essential for Glioblastoma Cancer Stem Cell Maintenance by Mario-Luca Suvà and 12 co-authors, including Ivan Stamenkovic, Cancer Res 2009(Dec 15); 69(24): 9211-8 [PubMed Citation][Connotea bookmark].


• Hypoxia-Regulated Delta-like 1 Homologue Enhances Cancer Cell Stemness and Tumorigenicity by Yuri Kim and 3 co-authors, including Zhong Yun, Cancer Res 2009(Dec 15); 69(24): 9271-80 [PubMed Citation][Connotea bookmark].


• Cancer Stem Cells and Aneuploid Populations within Developing Tumors Are the Major Determinants of Tumor Dormancy by Anjali P Kusumbe and Sharmila A Bapat, Cancer Res 2009(Dec 15); 69(24): 9245-53 [PubMed Citation][ResearchGATE entry].


• Stem-like cancer cells are inducible by increasing genomic instability in cancer cells by Yi Liang and 9 co-authors, including Yi-Xin Zeng, J Biol Chem 2009(Dec 9) [Epub ahead of print][PubMed Citation][Early version of full text].


• Gene set enrichment analysis provides insight into novel signalling pathways in breast cancer stem cells by Michiko Murohashi and 9 co-authors, including Noriko Gotoh, Br J Cancer 2009(Dec 8) [Epub ahead of print][PubMed Citation][ResearchGATE entry].


• Brain Tumor Cells Made More Responsive to Radiation, ScienceDaily, December 3, 2009 [Stem Cells 2009(Nov 17)]][PubMed Citation].


• SOM scientists explore spice as complementary treatment option for colorectal cancer, Prognosis E-news, Wayne State University School of Medicine, November 24, 2009 [Transl Oncol 2009(Dec);2(4):321-8][PubMed Citation].


• Is ALDH1 a good method for definition of breast cancer stem cells? by Veronique Neumeister and David Rimm, Breast Cancer Res Treat 2009(Nov 28) [Epub ahead of print][PubMed Citation][Connotea bookmark].


• Single-Cell STAT5 Signal Transduction Profiling in Normal and Leukemic Stem and Progenitor Cell Populations Reveals Highly Distinct Cytokine Responses by Lina Han and 5 co-authors, including Jan Jacob Schuringa, PLoS ONE 2009(Nov 24); 4(11): e7989 [PubMed Citation][Full text in PMC][Connotea bookmark].


• Recurrent hepatocellular carcinoma cells with stem cell-like properties: possible targets for immunotherapy by Xiaolan Xu‌ and 8 co-authors, including Zhiqian Zhang‌, Cytotherapy 2009(Nov 24) [Epub ahead of print][PubMed Citation][Connotea bookmark].

MK-0752 kills lingering breast CSC

Experimental Drug Kills Breast Cancer Stem Cells In Early Trials by Julie Steenhuysen, Reuters, December 11, 2009 [Another link][FriendFeed entry]. First two paragraphs:

An experimental drug was effective at killing breast cancer stem cells -- a kind of master cancer cell that resists chemotherapy, U.S. researchers said on Friday.

Studies in animals and women with advanced breast cancer showed the experimental compound MK-0752, under development by Merck & Co Inc (MRK.N), was able to kill off cancer stem cells that linger in the breast after chemotherapy.

The NCI Drug Dictionary entry for MK-0752:

A synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

SC-derived gene expression profiles predict poor outcome for AML patients

Leukemic and Normal Stem Cell Transcriptional Signatures Determined by Functional Assays Are Predictive of the Overall Survival of AML Patients by Kolja Eppert and 11 co-authors, including John E Dick, Abstract #389, 51st ASH Annual Meeting, December 7, 2009. Final sentence:

Together these data support the hypothesis that the biological determinants that underlie stemness in both normal and leukemic cells are predictors of poor outcome, and are potential targets for novel therapy.

Differences that separate normal vs cancer SC molecular circuitry

Pluripotent Transcription Factors Possess Distinct Roles in Normal versus Transformed Human Stem Cells by Junfeng Ji, Tamra E Werbowetski-Ogilvie, Bonan Zhong, Seok-Ho Hong and Mickie Bhatia, PLoS ONE 2009(Nov 30); 4(11): e8065 [FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

BACKGROUND: Cancer and normal stem cells (SCs) share proliferative properties of self-renewal and expression of key transcription factors (TFs). Despite similar TF identities, the functional role of specific TFs responsible for retaining SC state has yet to be examined in cancer. METHODOLOGY/PRINCIPAL FINDINGS: Here, we compare the role of Oct4 and Nanog, two-core pluripotent TFs, in transformed (t-hPSCs), and normal human pluripotent stem cells (hPSCs). Unlike normal SCs, self-renewal and survival of t-hPSCs were found to be independent of Oct4. In contrast, t-hPSCs exhibit hypersensitivity to reduction in Nanog and demonstrate complete loss of self-renewal coupled with apoptosis. Dual and sequential knockdown of Oct4 and Nanog revealed that sensitivity of t-hPSCs to Nanog was Oct4 dependent. CONCLUSIONS/SIGNIFICANCE: Our study indicates a bifurcation for the role of two-core SC and cancer related TFs in self-renewal and survival processes. We suggest that the divergent roles of these TFs establish a paradigm to develop novel therapeutics towards selective destruction of aggressive tumors harboring cancer stem cells (CSCs) with similar molecular signatures.

Twist modulates breast CSC

Potential new 'twist' in breast cancer detection, EurekAlert, December 4, 2009 [FriendFeed entry]. First paragraph:

Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called "Twist" may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

Based on: Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression by Farhad Vesuna, Ala Lisok, Brian Kimble and Venu Raman, Neoplasia 2009(Dec); 11(12): 1318-28 [Abstract][OA full text PDF][DOAJ entry for Neoplasia].

More about IMUC

ImmunoCellular (OTC: IMUC.OB) Notches Deal for New Cancer Stem Cell Vaccine Target by Mike Havrilla, BioMedReports, December 2, 2009. First paragraph:

In an option agreement announced today with MD Anderson Medical Center, ImmunoCellular Therapeutics (OTC: IMUC.OB) has acquired the rights to novel peptides that elicit a T-cell immune response against validated cancer stem cell targets known as the Notch and Numb pathways.

The same news item is also available via iStockAnalyst.

See also: ImmunoCellular Therapeutics Enters into Option Agreement with The University of Texas M. D. Anderson Cancer Center for a Novel Cancer Stem Cell Therapy, Business Wire, December 2, 2009.