Cancer Stem Cell News

Cancer Stem Cell Chronicle

2011-09-14T15:09:00.002-04:00

About 3 months ago, as an experiment, I launched the Cancer Stem Cell Chronicle, an online daily newspaper that's based on excerpts from 3 streams of content: 1) Twitter content tagged #cancerSC, 2) Twitter content that includes the keywords "cancer stem", and, 3) content derived from a PubMed RSS feed for the search term "cancer stem".

The experiment looks promising. The CSC Chronicle is beginning to provide a convenient way to monitor recent research news about cancer stem cells. Archives are available. The section headings in the CSC Chronicle aren't very meaningful, and should be ignored.

The CSC Chronicle is hosted by Paper.li.

A difference between normal and cancer SC biology in the nervous system

2011-01-06T11:29:00.003-05:00

Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition by Pedro Castelo-Branco and 12 co-authors, including Uri Tabori, Clin Cancer Res 2011(Jan 1); 17(1): 111-121 [Full text]. Translational Relevance:

Pediatric neural tumors (brain tumors and neuroblastoma) are the leading cause of morbidity and mortality in childhood cancer. This is due to their ability to recur after minimal disease is achieved. Telomerase is active in most malignant pediatric neural tumors. Therefore, telomerase inhibition may offer an effective treatment option for such patients. Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance.

This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo.

These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors.

For a commentary on this article, see: Anita B Hjelmeland and Jeremy N Rich, Clin Cancer Res 2011(Jan 1); 17(1): 3-5 (unlike the article, the commentary is not publicly accessible). Abstract:

Telomerase is an important mechanism by which cancers escape replicative senescence. In neural tumors, cancer stem cells express telomerase, suggesting that this may explain their preferential tumorigenesis. Oligonucleotide telomerase targeting selectively disrupts cancer stem cell growth through the induction of differentiation, adding to the armamentarium of anticancer stem cell therapies.

Two new initiatives from the CSCC

2010-12-19T16:41:00.001-05:00

The Cancer Stem Cell Consortium (CSCC) has announced the launch of two new initiatives for 2011-2012. Information about these initiatives is available via the websites of the CSCC and Genome Canada.

The two initiatives are:

1. C4Resource: The Canada-California Collaborative Cancer Stem Cell Resource and Technology Platform Network or C4Resource, which would coordinate cancer stem cell research resources and platform technologies more efficiently and effectively to advance research and discovery and accelerate clinical translation of new findings; and,

2. Partnership with CIRM: A second funding partnership with the California Institute for Regenerative Medicine (CIRM) through the CIRM's Disease Team Therapy Development Research Awards.

Information about the CIRM Disease Team Therapy Development Research Award RFA is available at: http://www.cirm.ca.gov/RFA_10-05

From the Editor

2010-10-07T19:19:00.000-04:00

I'll be taking some time away from blogging for the remainder of 2010. My tentative plan is to return with a different approach. For example, it may rely much less on blog posts, and more on short news items that can be found via a search of the real-time feed aggregator FriendFeed (FF) for the hashtag #cancerSC. An advantage of FF is that it permits news items and comments to be added by anyone who joins FriendFeed, and thus fosters a more community-oriented approach.

Trials to target CSCs

2010-10-02T09:44:00.004-04:00

U-M stem cell trial shows promise against breast cancer by Kim Kozlowski, The Detroit News, September 30, 2010. Excerpt:

The research will be highlighted next week in Detroit during the World Stem Cell Summit, a gathering of 1,200 prominent stem cell scientists, industry leaders and advocates from 30 countries.

OA Video Protocol from Matsui Lab

2010-10-02T08:55:00.002-04:00

Isolation of Stem Cells from Human Pancreatic Cancer Xenografts by Zeshaan Rasheed, Qiuju Wang, William Matsui, J Vis Exp 2010(Sep 26);(43). pii: 2169. OA Video Protocol.

Insights into the stem cells of CML

2010-09-24T19:46:00.002-04:00

Insights into the stem cells of chronic myeloid leukemia by I Sloma, X Jiang, A C Eaves and C J Eaves, Leukemia 2010(Sep 23). [Epub ahead of print][PubMed citation]. Abstract:

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis. In particular, these emphasize the need for new agents that effectively and specifically target CML stem cells to produce non-toxic, but curative therapies that do not require lifelong treatments.

Critical molecular pathways in CSCs of CML

2010-09-23T19:09:00.002-04:00

Critical molecular pathways in cancer stem cells of chronic myeloid leukemia by Y Chen, C Peng, C Sullivan, D Li and S Li, Leukemia 2010(Sep); 24(9): 1545-54. Epub 2010 Jun 24. [Connotea bookmark][PubMed citation][Full text]. The abstract of this OA review:

Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations resistant to kinase inhibitors. Development of curative therapies for CML requires the identification of crucial molecular pathways responsible for the survival and self-renewal of LSCs. In this review, we will discuss our current understanding of these crucial molecular pathways in LSCs and the available therapeutic strategies for targeting these stem cells in CML.

Must the last CML cell be killed?

2010-09-20T19:16:00.005-04:00

Do we have to kill the last CML cell? DM Ross, TP Hughes and JV Melo, Leukemia 2010(Sep 16) [Epub ahead of print][FriendFeed entry][PubMed citation][Full text]. The abstract of this OA review:

Previous experience in the treatment of chronic myeloid leukaemic (CML) has shown that the achievement of clinical, morphological and cytogenetic remission does not indicate eradication of the disease. A complete molecular response (CMR; no detectable BCR-ABL mRNA) represents a deeper level of response, but even CMR is not a guarantee of elimination of the leukaemic, because the significance of CMR is determined by the detection limit of the assay that is used. Two studies of imatinib cessation in CMR are underway, cumulatively involving over 100 patients. The current estimated rate of stable CMR after stopping imatinib is approximately 40%, but the duration of follow-up is relatively short. The factors that determine relapse risk are yet to be identified. The intrinsic capacity of any residual leukaemic cells to proliferate following the withdrawal of treatment may be important, but there may also be a role for immunological suppression of the leukaemic clone. No currently available test can formally prove that the leukaemic clone is eradicated. Here we discuss the sensitive measurement of minimal residual disease, and speculate on the biology of BCR-ABL-positive cells that may persist after effective therapy of CML.

On the low frequency of tumor-initiating cells

2010-09-08T19:31:00.004-04:00

Tumor-Initiating Cells Are Rare in Many Human Tumors by Kota Ishizawa and 16 co-authors, including Benjamin G Neel and William Matsui, Cell Stem Cell 2010(Sep 3); 7(3): 279-282. [FriendFeed entry][PubMed citation]. Abstract:

Tumor-initiating cells (TICs) are defined by their ability to form tumors after xenotransplantation in immunodeficient mice and appear to be relatively rare in most human cancers. Recent data in melanoma indicate that the frequency of TICs increases dramatically via more permissive xenotransplantation conditions, raising the possibility that the true frequency of TICs has been greatly underestimated in most human tumors. We compared the growth of human pancreatic, non-small cell lung, and head and neck carcinomas in NOD/SCID and NSG mice. Although TIC frequency was detected up to 10-fold higher in NSG mice, it remained low (<1 in 2500 cells) in all cases. Moreover, aldehyde dehydrogenase-positive (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate that TICs are rare in these cancers and that the identification of TICs and their frequency in other human malignancies should be validated via primary tumors and highly permissive xenotransplantation conditions.

Some breast cancer tumors may not originate from stem cells?

2010-09-04T20:04:00.004-04:00

Surprise breast cancer source by Jennifer Welsh,TheScientist.com, September 2, 2010. First paragraph:

Some breast cancer tumors may not originate from stem cells as previously believed, according to a study published in the September 3rd issue of Cell Stem Cell. The discovery is an important step in the development of treatments for these cancers.

This news story is based on the publication: BRCA1 Basal-like Breast Cancers Originate from Luminal Epithelial Progenitors and Not from Basal Stem Cells by Gemma Molyneux and 11 co-authors, including Matthew J Smalley, Cell Stem Cell 2010(Sep 3); 7(3): 403-417. OA article [Full text] [PubMed citation].

A commentary: Cancer Cell of Origin: Spotlight on Luminal Progenitors by Christine L Chaffer and Robert A Weinberg, Cell Stem Cell 2010(Sep 3); 7(3): 271-272. [PubMed citation].

Isolation and killing of candidate CML stem cells by antibody targeting

2010-09-04T19:03:00.002-04:00

Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein by Marcus Järås and 10 co-authors, including Thoas Fioretos, Proc Natl Acad Sci USA 2010(Aug 30). OA article. [Epub ahead of print][PubMed citation]. Abstract:

Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 and giving rise to the constitutively active tyrosine kinase P210 BCR/ABL1. Therapeutic strategies aiming for a cure of CML will require full eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a consequence of retroviral BCR/ABL1 expression. To test whether IL1RAP expression distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate their Ph-chromosome status. Interestingly, we found that the CML CD34(+)CD38(-)IL1RAP(+) cells were Ph(+), whereas CML CD34(+)CD38(-)IL1RAP(-) cells were almost exclusively Ph(-). By performing long-term culture-initiating cell assays on the two cell populations, we found that Ph(+) and Ph(-) candidate CML stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34(+)CD38(-) cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell surface biomarker distinguishing Ph(+) from Ph(-) candidate CML stem cells and opens up a previously unexplored avenue for therapy of CML.

Two Open Access reviews

2010-08-23T15:18:00.009-04:00

1) Cancer Stem Cells in Pancreatic Cancer by Qi Bao and 6 co-authors, including Karl-Walter Jauch and Christiane J Bruns, Cancers 2010(Aug 19); 2(3): 1629-41. [Full text PDF][Scribd entry][Part of the Special Issue Pancreatic Cancer]. Abstract:

Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

2) The Emerging Role of the Phosphatidylinositol 3-Kinase/ Akt/Mammalian Target of Rapamycin Signaling Network in Cancer Stem Cell Biology by Alberto M Martelli and 4 co-authors, including James A McCubrey, Cancers 2010(Aug 18); 2(3): 1576-96. [Part of the Special Issue Cancer Stem Cells].

Comment: Review #2 is the first paper that has been published in the special issue on Cancer Stem Cells. As of August 20, 17 more contributions to this special issue are planned. Review #1, although about CSCs, is a contribution to a separate special issue on Pancreatic Cancer.

Selective targeting of neuroblastoma tumour-initiating cells

2010-08-19T19:32:00.005-04:00

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens by Kristen M Smith and 16 co-authors, including David R Kaplan, EMBO Mol Med 2010(Aug 18) [Epub ahead of print][Full text]. Abstract:

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.

See also: New Twist on Drug Screening to Treat Common Childhood Cancer, ScienceDaily, August 18, 2010. Excerpt:

A study led by scientists at The Hospital for Sick Children (SickKids) reveals a new method of identifying drugs to treat children suffering from fatal cancers for which an effective treatment has not been found. Rather than developing a new drug from scratch, which is a complicated and time-consuming process, they tried a different approach: in the lab, they tested existing drugs on cancer stem cells from young patients with neuroblastoma, one of the common cancers of infants and children.

A related blog post is: High-throughput cancer stem cell-based screening assay for therapeutic compounds by Alexey Bersenev, Stem Cell Assays, August 19, 2010 [FriendFeed entry].

Therapeutic implications of colon CSCs

2010-08-18T19:53:00.003-04:00

Therapeutic implications of colon cancer stem cells by Eros Fabrizi and 3 co-authors, including Lucia Ricci-Vitiani, World J Gastroenterol 2010(Aug 21); 16(31): 3871-7. OA review. [FriendFeed entry][PubMed citation]. Abstract:

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.

Putative tumor-initiating progenitor cells predict poor lung cancer prognosis

2010-08-18T19:19:00.005-04:00

Adult lung stem cells, vital to injury repair, associated with poor cancer prognosis, News release, UCLA Newsroom, August 17, 2010. Excerpts:

Adult stem cells that are vital for airway repair in the lung but that persist in areas where pre-cancerous lesions are found are associated with a poor prognosis in patients who develop cancer, even those with early-stage disease, researchers at UCLA's Jonsson Comprehensive Cancer Center have found.

.....

In this study, Gomperts and her team screened around 900 tumors removed from patients with non-small cell lung cancer at UCLA and the University of Texas' MD Anderson Cancer Center, looking to see whether the adult stem cells could be found in the tumor. In her lab, Gomperts is now studying the pre-cancerous lesions where the adult stem cells persist in an attempt to uncover the cascade of molecular events that may transform these cells into lung cancer stem cells.

The news release is based on this publication: Presence of a Putative Tumor-Initiating Progenitor Cell Population Predicts Poor Prognosis in Smokers with Non–Small Cell Lung Cancer by Aik T Ooi and 19 co-authors, including Brigitte N Gomperts, Cancer Res 2010(Aug 15); 70(16): 6639-48. [PubMed citation][Full text]. Abstract:

Smoking is the most important known risk factor for the development of lung cancer. Tobacco exposure results in chronic inflammation, tissue injury, and repair. A recent hypothesis argues for a stem/progenitor cell involved in airway epithelial repair that may be a tumor-initiating cell in lung cancer and which may be associated with recurrence and metastasis. We used immunostaining, quantitative real-time PCR, Western blots, and lung cancer tissue microarrays to identify subpopulations of airway epithelial stem/progenitor cells under steady-state conditions, normal repair, aberrant repair with premalignant lesions and lung cancer, and their correlation with injury and prognosis. We identified a population of keratin 14 (K14)-expressing progenitor epithelial cells that was involved in repair after injury. Dysregulated repair resulted in the persistence of K14+ cells in the airway epithelium in potentially premalignant lesions. The presence of K14+ progenitor airway epithelial cells in NSCLC predicted a poor prognosis, and this predictive value was strongest in smokers, in which it also correlated with metastasis. This suggests that reparative K14+ progenitor cells may be tumor-initiating cells in this subgroup of smokers with NSCLC.

Partnership Pays Off

2010-08-16T15:09:00.003-04:00

Northern Exposure by Emmet Pierce, San Diego Business Journal, August 16, 2010. Excerpt:

An example of San Diegans collaborating with Canadians is the work that has taken place at the UC San Diego Moores Cancer Center in cooperation with research at the University of Toronto. The partnership has enabled San Diego researchers to acquire a $20 million grant to develop drugs to be used against leukemia stem cells, Barr says.Dr. Catriona Jamieson, director of the stem cell research program at the Moores center, said scientists from Toronto and San Diego share "a deep and abiding interest in cancer stem cell biology." The Canadian consulate in San Diego was instrumental in helping to create a relationship in which both institutions would benefit, sharing information and applying for funds to support their research.

"The idea was to establish a Canada-California cancer stem cell initiative and obtain connections with Canadian funding agencies, particularly Genome Canada and the Ministry of Health," she said.

Jamieson added, "The most important thing is it allows people with disparate abilities and backgrounds to work together on the same problem."

Barr said the University of Toronto also was able to secure a $20 million research grant because of the collaboration, "so the team is greater than the sum of its parts."

Oxygen, hypoxia and the stem cell niche

2010-08-06T18:55:00.005-04:00

Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche by Ahmed Mohyeldin, Tomás Garzón-Muvdi and Alfredo Quiñones-Hinojosa, Cell Stem Cell 2010(Aug 6); 7(2): 150-61. Review. [PubMed citation][FriendFeed entry]. Via Twitter @CellStemCell: Access [to the full text] is free in August worldwide so readers can try out new enhanced online format.

Abstract:

The defining hallmark of stem cells is their ability to self-renew and maintain multipotency. This capacity depends on the balance of complex signals in their microenvironment. Low oxygen tensions (hypoxia) maintain undifferentiated states of embryonic, hematopoietic, mesenchymal, and neural stem cell phenotypes and also influence proliferation and cell-fate commitment. Recent evidence has identified a broader spectrum of stem cells influenced by hypoxia that includes cancer stem cells and induced pluripotent stem cells. These findings have important implications on our understanding of development, disease, and tissue-engineering practices and furthermore elucidate an added dimension of stem cell control within the niche.

Cell of origin for human prostate cancer

2010-07-31T12:26:00.002-04:00

Scientists at UCLA find cell of origin for human prostate cancer by Kim Irwin, UCLA Newsroom, July 29, 2010. Excerpts:

"Certainly, the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells," said Witte, senior author of the study and a Howard Hughes Medical Institute Investigator. "But we were able to start with a basal cell and induce human prostate cancer, and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell-signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy."

.....

The new human-in-mouse model system developed in the study was created by taking healthy human prostate tissue that will induce cancer once it is placed in mice, instead of taking malignant tissue that is already cancerous and implanting it. This model can now be used to evaluate the effectiveness of new types of therapeutics. By using defined genetic events to activate specific signaling pathways, researchers can more easily compare therapeutic efficacy. The new model, by deconstructing tissue and then reconstructing it, also will aid in analyzing how the cells change during cancer progression.

This news release is based on the publication: Identification of a Cell of Origin for Human Prostate Cancer by Andrew S Goldstein and 5 co-authors, including Owen N Witte, Science 2010(Jul 30); 329(5991): 568-71. [PubMed citation][FriendFeed entry][Twitter trackbacks via Topsy].

Disagreement about melanoma CSCs

2010-07-28T19:40:00.004-04:00

The Evolving Science of Cancer Stem Cells by Carmen Phillips, NCI Cancer Bulletin 2010(Jul 27); 7(15). Excerpt:

Researchers from Stanford University earlier this month reported in Nature that they had found a marker, CD271, that identified a somewhat unique population of cells that could produce melanoma in highly immunocompromised mice; anywhere from 2.5 percent to 41 percent of cells in their human tumor samples expressed the marker. In additional experiments using similar mice on which human skin was engrafted, only tumor cells with the marker could produce tumors and metastases in the mice. (In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells.)

The publication about CD271 is: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 colleagues, Nature 2010(Jul 1); 466(7302): 133-7. [PubMed citation].

Comments: The sentence: "In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells" is noteworthy. Why the difference in results for CD271?

The publication by Boiko and co-authors was cited in a previous post to this blog, "Melanoma-initiating cells identified", dated July 1, 2010.

See also an earlier post to this blog, "Tumorigenic cells not rare in human melanoma", dated December 3, 2008.

Researchers Study CSCs as Therapeutic Targets for Mesothelioma

2010-07-27T19:36:00.004-04:00

Researchers Study Cancer Stem Cells as Therapeutic Targets for Mesothelioma, Asbestos.com, July 26, 2010. Excerpt:

In a study published in the International Journal of Oncology, Cortes-Dericks and colleagues tested whether cancer stem cells in malignant pleural mesothelioma express resistance to cisplatin and pemetrexed, two chemotherapy drugs commonly used to treat mesothelioma cancer.

This news item is based on the OA publication entitled: Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed by Lourdes Cortes-Dericks, Giovanni L Carboni, Ralph A Schmid and Golnaz Karoubi, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

Prostate CSCs sensitive to gamma-tocotrienol?

2010-07-26T11:38:00.007-04:00

Gamma-Tocotrienol Kills Prostate Cancer Stem Cells, PRNewswire, July 25, 2010. Excerpt:

The scientists found that low doses of gamma-tocotrienol cause apoptosis in the prostate cancer stem cells and suppress their colony formation capability. This results in a lower prostate cancer stem cell population (as defined by the protein markers CD133 and CD44). Further tests in mice models were conducted, where mice implanted with hormonal refractory prostate cancer cells were given gamma-tocotrienol orally. The results showed that gamma- tocotrienol not only reduced tumour size formed, but also decreased the incidence rate of tumour formation by 75%, as compared to the control group of mice, which had 100% tumour formation. These results strongly suggest that gamma-tocotrienol could be developed for prostate cancer prevention and treatment.

The news release by Davos Life Science is based on the publication:

Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population by Sze Ue Luk and 11 co-authors, including Ming-Tat Ling, Int J Cancer 2010(Jul 8) [Epub ahead of print][PubMed citation].

Comment:

See also a relevant patent application: (WO/2010/047663) Use of Tocotrienol Composition for the Prevention of Cancer.
Publication Date: 29.04.2010
Applicants: DAVOS LIFE SCIENCE PTE. LTD. [SG/SG]; 16 Tuas South Street 5 Singapore 637795 (SG) (All Except US).
LING, Ming Tat [CN/AU]; (AU) (US Only).
YAP, Wei Ney [MY/SG]; (SG) (US Only).
WONG, Yong Chuan [MY/CN]; (CN) (US Only).
YAP, Yee Leng, Daniel [MY/SG]; (SG) (US Only).

Irradiating brain's stem cell niche

2010-07-25T10:26:00.004-04:00

Irradiating brain's stem cell niche doubles survival time for patients with brain cancers by Kim Irwin, News Release, UCLA Newsroom, July 23, 2010. Excerpt:

Patients with deadly glioblastomas who received high doses of radiation that hit a portion of the brain which harbors neural stem cells had double the progression-free survival time as patients who had lower doses or no radiation targeting the area, a study from the radiation oncology department at UCLA's Jonsson Comprehensive Cancer Center has found.

The news release is based on this OA publication: Irradiation of the Potential Cancer Stem Cell Niches in the Adult Brain Improves Progression-free Survival of Patients with Malignant Glioma by Patrick Evers and 6 co-authors, including Frank Pajonk, BMC Cancer 2010(Jul 21); 10(1):384. [Epub ahead of print][FriendFeed entry].

Comment: On the brain as a model system to study the impact of radiation dose given to stem cell niches. Provides clinical evidence, based on an improvement in progression-free survival, to support the hypothesis that higher radiation doses to neural stem cell (NSC) niches improves patient survival by eradicating CSCs.

More about salinomycin

2010-07-18T11:15:00.008-04:00

New mission for salinomycin in cancer by Cord Naujokat, SciTopics, July 15, 2010. Excerpt (in the "continue reading" section):

In addition, a very recent study demonstrates that salinomycin overcomes ATP-binding cassette (ABC) transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like cells (3).

Reference #3: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells, by Dominik Fuchs and 4 co-authors, including Cord Naujokat, Biochem Biophys Res Commun 2010(Apr 16);394(4): 1098-104 [Epub 2010(Mar 27)][PubMed citation].

Comments: Near the end of this article about salinomycin is the comment that "the investigation of its safety, toxicity, pharmacology and anticancer activity in humans will be a challenge." The author then mentions a preliminary study of "a small cohort of patients with metastatic breast cancer or metastatic head and neck cancers". The results of this preliminary study of the toxicity of salinomycin are summarized. They have not yet been published in the peer-reviewed literature, although a manuscript has been submitted [see reference #4 in the article]. The implication of these preliminary results is that there may be a "therapeutic window" for salinomycin, that is, a drug dosage that yields clinically significant benefits in the absence of excessive toxicity.

For a previous commentary on salinomycin, see: Cancer stem cell breakthrough by Kat Arney, Science Update blog, Cancer Research UK, August 14, 2009. Excerpt:

We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans. Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

If there is a "therapeutic window" for salinomycin, it could be a small one, and is likely to vary from one tumor to another.

For a previous post to this blog about salinomycin, see: Identification of selective inhibitors of breast CSCs in mice, August 14, 2009.

Innovative Researcher Vlog

2010-07-15T12:41:00.007-04:00

SU2C Innovative Researcher Vlog: Dr. Lawlor (Pt. 3). Video (3:09 min) posted July 13, 2010. Features Elizabeth R Lawlor, University of Michigan, an SU2C Innovative Research Grants Investigator. [About SU2C (Stand Up to Cancer)]. She provides brief comments about her project: "Modeling Ewing Tumor Initiation in Human Neural Crest Stem Cells". How do normal stem cells become cancer stem cells?

An example of a recent (OA) publication from her laboratory: CD133 expression in chemo-resistant Ewing sarcoma cells by
Xiaohua Jiang and 8 co-authors, including Elizabeth R Lawlor,
BMC Cancer 2010(Mar 26); 10: 116. [FriendFeed entry][PubMed citation][Full text via PMC].

Two recent OA articles

2010-07-11T19:37:00.002-04:00

Two articles, with Open Access (OA) to the full text (PDF):

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance, Oncol Rep 2010(Aug); 24(2): 501-5. [PubMed citation].

Comment about these journals:

Spandidos Publications publishes six journals. Of these six, two are: International Journal of Oncology (2009 Impact Factor: 2.4) and Oncology Reports (2009 Impact Factor: 1.6). This publisher provides a hybrid open access option. The Information for Authors for all six journals includes, at the bottom of the page, this information: "Should authors prefer or require their article to be freely available as soon as it has been published, they may request open access immediately upon publication for a fee of EUR 450."

CSC news update 2010-07-03

2010-07-03T10:53:00.007-04:00

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Cancer Stem Cells Are Not 'One Size Fits All,' Lung Cancer Models Show http://bit.ly/bE9F0V & http://bit.ly/amEkFR. Hashtag: #cancerSC. Posted to Twitter on Fri Jul 02 via TweetDeck

Melanoma-initiating cells identified

2010-07-01T15:53:00.010-04:00

Melanoma-initiating cells identified by study by Krista Conger, News release, Stanford School of Medicine, June 30, 2010. Excerpt:

Scientists at the School of Medicine have identified a cancer-initiating cell in human melanomas. The finding is significant because the existence of such a cell in the aggressive skin cancer has been a source of debate. It may also explain why current immunotherapies are largely unsuccessful in preventing disease recurrence in human patients.

The news release is about this publication: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 co-authors, including Irving L. Weissman, Nature 2010(Jul 1); 466(7302): 133-7. [FriendFeed entry].

A blog post about this same publication is: Stanford scientists identify a melanoma-initiating cell by Krista Conger, Scope blog, Stanford School of Medicine, June 20, 2010.

See also a commentary about the publication: Cancer stem cells: Invitation to a second round by Peter Dirks, Nature 2010(Jul 1); 466(7302): 40-1. Excerpt:

Boiko et al. study a type of human skin cancer called melanoma and, in particular, cancer cells enriched in a stem-cell marker called CD271. They find that, unlike other cells from the same tumour, CD271-expressing (CD271+) cells could initiate and maintain tumour growth in vivo — an observation consistent with the existence of a melanoma-cell functional hierarchy.

This finding reflects a view different from that of an earlier study by Quintana et al.[3], which demonstrated that, in some cases, as many as 50% of human melanoma cells have tumorigenic potential. In addition, no marker tested identified a tumorigenic subpopulation. The authors[3] concluded that the frequency of cancer cells that can initiate tumorigenesis depends, in part, on the assessment techniques and assays.

Another news item, based on the same publication, is: New hope in fight against skin cancer as deadly 'master cells' are identified for first time, Mail Online, July 1, 2010. Excerpt:

However Dr Alexander Boiko, who made the discovery at Stanford University, said the newly discovered 'stem cells' in advanced skin cancers were often missed by conventional immunotherapy.

'Without wiping out the cells at the root of the cancer, the treatment will fail,' he said.

Comments: Boiko et al. and Dirks suggest reasons why results different from those of Quintana et al. were obtained. One possibility is that the melanomas that the latter authors studied were at an advanced stage. If, as a cancer progresses, more cells acquire the attributes of cancer stem cells, then advanced melanomas may contain very high frequencies of tumorigenic cells.

As Boiko et al. point out in their publication, "The most crucial test of the tumour stem cell hypothesis is that markers or pathways restricted to tumour stem cells can be targets for curative therapies in the patient, which has not yet been done."

CSC news update 2010-06-26

2010-06-26T12:40:00.000-04:00

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Max Wicha: Breast cancer stem cells (4 min video) http://bit.ly/bhoNWn (via @cells_nnm). Hashtag: #cancerSC. Posted to Twitter on Fri Jun 25, 2010 via TweetDeck

On glioma recurrence and CSCs

2010-06-26T12:13:00.002-04:00

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.

OncoMed Has 'Wnt' in its Sails

2010-06-20T10:51:00.006-04:00

OncoMed Has 'Wnt' in its Sails; Bayer Deal Adds $40M Up Front by Jennifer Boggs, Bioworld, June 18, 2010. Excerpts:

[OncoMed's] latest accomplishment is another early stage deal, this time with Bayer Schering Pharma AG, to develop drugs targeting the Wnt signaling pathway. It's an agreement that brings $40 million up front, with the potential for more than $1 billion in future milestones.

.....

The Wnt pathway is believed to be a key target in halting cancer stem cell activity. But only a few other firms - Avalon Pharmaceuticals Inc. (now part of Clinical Data Inc.) and 2008 start-up Wintherix LLC, for example - have entered that space, largely because Wnt is not an easily druggable target.

News release from Bayer: Bayer Schering Pharma and OncoMed Pharmaceuticals Enter Strategic Alliance to Develop Anti-Cancer Stem Cell Therapeutics, June 17, 2010. Excerpt:

Bayer Schering Pharma AG, Germany, and OncoMed Pharmaceuticals, Inc., today announced a global strategic alliance to discover, develop and commercialize novel anti-cancer stem cell therapeutics targeting the Wnt signaling pathway. Cancer stem cells are a subset of tumor cells believed to play a significant role in the establishment, metastasis and recurrence of cancer and agents targeting the Wnt pathway have the potential to be developed as pan-tumor drugs.

Comment: The Bayer-OncoMed strategic alliance has received attention via the social media. See, for example, the results of this FriendFeed search.

CIRM and Wisconsin sign a Declaration of Cooperation

2010-06-18T09:32:00.001-04:00

Wisconsin Governor Jim Doyle and California’s State Stem Cell Agency Sign Declaration Of Cooperation to Advance Stem Cell Research toward Cures, News release, California Institute For Regenerative Medicine (CIRM), June 17, 2010. Excerpts:

The California Institute for Regenerative Medicine (CIRM) and the state of Wisconsin, coordinated through and led by the University of Wisconsin-Madison, expect to identify opportunities to further the advancement, promotion and funding of stem cell research and the development of stem cell therapies.

.....

CIRM currently has similar agreements with the Cancer Stem Cell Consortium of Canada, the State of Victoria in Australia, the JST in Japan, the MICINN in Spain, the MRC in the United Kingdom, the BMBF in Germany, MOST in China and the state of Maryland, and the New York Stem Cell Foundation.

Patent application: Levels of Oct1 as a method of identifying CSCs

2010-06-17T20:07:00.003-04:00

(WO2010065400) Cancer Biomarker and Methods of Using Thereof.

Excerpt from PCT Biblio. Data:

International Application No.: PCT/US2009/065742
Publication Date: 10.06.2010

Excerpt from Description:

Described herein are biomarkers which can be used for identifying a subject at risk for or evaluating the progression of cancer. In certain aspects, these biomarkers can be used to identify cancer stem cells. These biomarkers can include Octl or molecular variants thereof and downstream targets of Octl. In addition, described herein are methods for reducing the expression of these biomarkers associated with cancer.

Decitabine may target ovarian CSCs?

2010-06-13T19:11:00.002-04:00

Two-Drug Phase I Trial Shows Promise in Treating Late-Stage Ovarian Cancer, ScienceDaily, June 13, 2010. Excerpt:

"Our hypothesis is that decitabine isn't just targeting active ovarian cancer cells, but also cancer stem cells that seem to survive the first treatments," [Kenneth] Nephew said. "By keeping tumor suppression genes from being methylated, carboplatin and other platinum-based treatments for ovarian cancer have a better chance of success in the late stages."

This news release is about the publication entitled: A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer by Fang Fang, Curt Balch and 9 co-authors, including Kenneth P Nephew and Daniela E Matei, Cancer 2010(Jun 8) [Epub ahead of print].

CSC news update 2010-06-13

2010-06-13T12:39:00.008-04:00

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Wellcome Trust - award to PTC Therapeutics, to combat drug-resistant cancers http://bit.ly/cJpUie. Hashtag: #cancerSC. Posted to Twitter on Wed Jun 09, 2010 via TweetDeck

CSCs responsible for metastasis identified

2010-06-05T19:16:00.006-04:00

Cancer stem cells responsible for metastasis identified: HK study, Xinhua News Agency, June 4, 2010. Excerpt:

Hong Kong researchers have identified a subset of cancer stem cells responsible for metastasis in human colorectal cancer which can help better predict the prognosis and design a more suitable treatment for patients, according to a study made public by the University of Hong Kong on Friday.

The researchers from the university's medicine school discovered that cancer stem cells with a surface marker CD26, which marks a subset of cancer stem cells with metastatic capacity, are present in all terminal colon cancer cells and all metastatic cancer cells.

This news item is about the publication: A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer by Roberta Pang and 13 co-authors, including Wai Lun Law, Ronnie T Poon and Benjamin CY Wong [photos of authors], Cell Stem Cell 2010(Jun 4); 6(6): 603-15. [Summary][Twitter entry][Commentary][FriendFeed entry][Science Pond entry].

Phase I clinical trial of ICT-107

2010-06-02T19:29:00.006-04:00

Immune response correlation with progression-free survival in glioblastoma following dendritic cell immunotherapy (ICT-107) by Surasak Phuphanich and 9 co-authors, including Manish Singh, Keith Black and John Wu, J Clin Oncol 28:7s, 2010 (suppl; abstr 2097). To be presented at the 2010 ASCO Annual Meeting, June 06, 2010.

Related news releases:

ImmunoCellular Therapeutics Ltd. (IMUC) to Present Cancer Vaccine Candidate, International Business Times, June 02, 2010. Excerpt:

Data from the company’s recent clinical trial of ICT-107, the company’s dendritic cell-based cancer vaccine candidate, will be presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) June 4-8 in Chicago.

See also: Immunocellular brain cancer vaccine shows promise, Reuters, June 02, 2010. Excerpt:

"We are targeting specific antigens that are on cancer stem cells ... the only population of cells that can really propagate a tumor," said Dr. John Yu, director of surgical neuro-oncology at Cedars-Sinai Medical Center in Los Angeles and ImmunoCellular's chief scientific officer.

Another related news release: Immunocellular Therapeutics Enters into Research Agreement with University of Pennsylvania to Support Phase II Clinical Trial of ICT-107, Business Wire, April 21, 2010.

Patent application involving miRNAs and CSCs

2010-05-27T15:51:00.004-04:00

Methods and Compositions Involving miRNAs in Cancer Stem Cells, Patent Application WO/2010/056737. [FriendFeed entry].

One of the applicants is Mirna Therapeutics, Inc.

CSC news update 2010-05-24

2010-05-24T19:10:00.009-04:00

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Markers on xenograft-initiating cells in estrogen receptor-negative breast cancer http://bit.ly/9Xhzbp. Hashtag: #cancerSC. Posted to Twitter on Fri May 21, 2010 via TweetDeck. [PubMed Citation]

An evolving concept of CSCs in tumor biology

2010-05-20T19:29:00.006-04:00

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].

US Patent: Isolation and use of solid tumor stem cells

2010-05-17T20:08:00.009-04:00

Isolation and use of solid tumor stem cells, United States Patent 7,713,710. [FreePatentsOnline][PatentStorm].
Publication Date: May 11, 2010.
Inventors: Clarke; Michael F. (Ann Arbor, MI), Morrison; Sean J. (Ann Arbor, MI), Wicha; Max S. (Ann Arbor, MI), Al-Hajj; Muhammad (Ann Arbor, MI).
Assignee: The Regents of the University of Michigan (Ann Arbor, MI) .
Appl. No.: 11/753,191
Filed: May 24, 2007
Abstract:

A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Parent Case Text:

CLAIM OF PRIORITY
This application is a Continuation of U.S. patent application Ser. No. 11/150,073, filed Jun. 10, 2005, which is a Continuation of U.S. patent application Ser. No. 09/920,517, filed Aug. 1, 2001, now U.S. Pat. No. 6,984,522, which claims priority to U.S. provisional applications Ser. No. 60/222,794, filed Aug. 3, 2000, and Ser. No. 60/240,317, filed Oct. 13, 2000, all of which are herein incorporated by reference in their entireties.

Google patents entry for Application Number 11/753,191 (The application that led to patent 7,713,710. The filing date was 24 May 2007).

Google patents entry for Application Number 11/150,073 (See Parent Case Text above: the filing date was 10 June 2005).

Google patents entry for Patent Number 6,984.522 (See Parent Case Text above: the filing date was 1 August, 2001 and the issue date was 10 Jan 2006). [FreePatentsOnline][PatentStorm].

Comment:

Not mentioned in the Parent Case Text above is United States Patent 7,115,360. [FreePatentsOnline][PatentStorm]. This patent was issued October 3, 2006 and filed on August 2, 2001.

The Parent Case Text for patent 7,115,360:

CLAIM OF PRIORITY
This patent is the United States national stage of PCT patent application PCT/US01/24243, published Feb. 14, 2002 as WO 02/12447, which is a continuation of U.S. Ser. No. 09/920,517, filed Aug. 1, 2001, now U.S. Pat. No. 6,984,522. This patent also claims priority to provisional patent applications U.S. Ser. Nos. 60/222,794, filed Aug. 3, 2000, and 60/240,317, Oct. 13, 2000.

Information about this patent was found via a Google search for "Isolation and use of solid tumor stem cells".

Generic drug a potential treatment for glioblastoma?

2010-05-13T13:01:00.008-04:00

DCA research on brain cancer, EurekAlert, May 12, 2010. [FriendFeed entry]. Excerpt: "... the orphan generic drug Dichloroacetate (DCA) may hold promise as potential therapy for ... a form of brain cancer called glioblastoma". Another excerpt:

By extracting glioblastomas from 49 patients over a period of 2 years and studying them within minutes of removal in the operating room, the team showed that tumors respond to DCA by changing their metabolism. Then, the team treated 5 patients with advanced glioblastoma and secured tumor tissues before and after the DCA therapy. By comparing the two, the team showed that DCA works in these tumors exactly as was predicted by test tube experiments. This is very important because often the results in non-human models tested in the lab do not agree with the results in patients. In addition, the team showed that DCA has anti-cancer effects by altering the metabolism of glioblastoma cancer stem cells, the cells thought responsible for the recurrences of cancer.

And,

No conclusions can be made on whether the drug is safe or effective in patients with this form of brain cancer, due to the limited number of patients tested by the study's leads Drs Michelakis and Petruk. Researchers emphasize that use of DCA by patients or physicians, supplied from for-profit sources or without close clinical observation by experienced medical teams in the setting of research trials, is not only inappropriate but may also be dangerous. ...

See also: Generic drug may be potential treatment for deadly brain cancer: U of A medical study by Noreen Remtulla and Julia Necheff, ExpressNews, University of Alberta, May 12, 2010.

And: Potential brain-cancer drug shows promise, CBC News, May 12, 2010. [CBC video].

And: Cancer drug trial raises hopes by Elise Stolte, Edmonton Journal, May 13, 2010.

These news reports are about the publication: Metabolic Modulation of Glioblastoma with Dichloroacetate by Evangelos D Michelakis and 12 co-authors, including Kenneth C Petruk, Sci Transl Med 2010(May 12); 2(31): 31ra34.

See also an editorial: Targeting Cell Metabolism in Cancer Patients by Matthew G Vander Heiden, Sci Transl Med 2010(May 12); 2(31) :31ed1. From the TOC: "Dichloroacetate can safely modify glucose metabolism in aggressive brain tumors when administered to patients". Last sentence of the editorial: "Time will tell whether this strategy constitutes an effective cancer therapy".

Comments: After an initial research publication in January 2007 [PubMed citation], DCA attracted much attention. See, for example, the Wikipedia entry for Dichloroacetic acid. And, Cancer society warns of untested drug, CBC News, March 22, 2007.

The Official University of Alberta DCA Website provides FAQs about DCA. It includes, in the News & Updates section, DCA Research Team publishes results of Clinical Trials (dated May 12, 2010) and an earlier Letter from Dr. Evangelos Michelakis (dated October 2008).

CSC news links 2010-05-08

2010-05-08T06:25:00.023-04:00

For links to recent news items about CSC, visit this [Topsy] page. Examples of two news items that have received attention in the past week:

New research links ovarian hormones with breast stem-cell growth - Globe and Mail http://bit.ly/brT71E. Hashtag: #cancerSC. Posted to Twitter on Wed May 06, 2010 via TweetDeck. [PubMed Citation]

Broccoli compound limits breast cancer (about sulforaphane) http://bit.ly/9blnNP & http://bit.ly/aOTSDv. Hashtag: #cancerSC. Posted to Twitter on Wed May 05, 2010 via TweetDeck. [PubMed Citation]

CSC news links 2010-05-01

2010-05-01T13:53:00.006-04:00

For links to recent news items, visit these [Twitter] or [FriendFeed] pages. Examples of two news items that have received attention:

Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers by Shan Deng and 15 co-authors, including George Coukos and Lin Zhang, PLoS ONE, 2010(Apr 21); 5(4): e10277 [Connbotea bookmark][PubMed Citation][OA full text]. Last sentence of the abstract:
As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.
AACR: Are Cancer Stem Cells Vulnerable to Trastuzumab? By Ed Susman, MedPage Today (Apr 19) [FriendFeed entry][AACR10 abstract]. Excerpt:
Mathematical modeling suggests that even in women whose breast cancer does not overexpress the HER-2 gene, treatment with trastuzumab (Herceptin) in the adjuvant setting could wipe out cancer stem cells, researchers reported here.

Sessions on CSC Therapeutics at AACR10

2010-04-26T18:53:00.003-04:00

There were two poster sessions on Cancer Stem Cell Therapeutics at the 101st Annual Meeting of the American Association for Cancer Research (AACR). The sessions, Cancer Stem Cell Therapeutics 1 and Cancer Stem Cell Therapeutics 2, took place on the morning and afternoon of April 20, 2010 [FriendFeed entry].

Two posters presented in the 2nd session have been highlighted in a news release. See: Alchemia’s HyACT Technology Enhances the Killing of Cancer Stem Cell Populations in Breast and Colorectal Cancer, Business Wire, April 20, 2010 [FriendFeed entry]. One of these is Poster #4293: Evaluation of activated CD44 as a biological target in the eradication of breast cancer stem cells, by Vera J Evtimov and Tracey J Brown [Presentation Abstract]. The other is Poster #4278: HA-Irinotecan targeting of activated CD44 is an effective therapy for the eradication of putative colon cancer stem cells [Presentation Abstract].

CSC news links 2010-04-18

2010-04-18T12:16:00.003-04:00

For links to recent news items, visit these [Twitter] or [FriendFeed] pages. Examples of a few news items that have received attention:

Split ends in CML: divergent roles of Hes1 by Catriona Jamieson, Blood 2010(Apr 8); 115(14): 2726-7 [FriendFeed entry][Connotea bookmark][PubMed citation][Full text PDF]. A comment on: Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia by Fumio Nakahara and 13 co-authors, Blood 2010(Apr 8); 115(14): 2872-81. [Epub 2009(Oct 27)][PubMed citation].

Metabolism and the leukemic stem cell by Omar Abdel-Wahab and Ross L Levine, J Exp Med 2010(Apr 12); 207(4): 677-80 [Epub 2010(Apr 5)][FriendFeed entry][ResearchGATE entry][CiteULike entry][Connotea bookmark][PubMed citation][Full text].

A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2alpha by Sascha Seidel and 13 co-authors, including Till Acker, Brain 2010(Apr); 133(Pt 4): 983-95 [FriendFeed entry][ResearchGATE entry][Connotea bookmark][PubMed citation].

MicroRNA therapy could be a powerful tool to correct the CSC dysregulation?

2010-04-16T19:51:00.002-04:00

Medical Hypothesis: No small matter: microRNAs - key regulators of cancer stem cells by Qing Ji, David Karnak, Ping Hao, Rongquan Wang and Liang Xu, Int J Clin Exp Med 2010(Mar 12); 3(1): 84-7 [FriendFeed entry][Connotea bookmark][Full text via PMC]. PubMed Abstract:

Emerging evidence demonstrates that both tumor suppressor and oncogenic miRNAs play an essential role in stem cell self-renewal and differentiation by negatively regulating the expression of certain key genes in stem cells. It seems logical that they may also be critical players in cancer stem cells. Though small in size, miRNAs play a key role in the epigenetic regulation of cancer stem cells. Specifically, the imbalance of oncogenic vs. tumor suppressor miRNAs may lead to dysregulation of cancer stem cells, thus causing excessive self-renewal and survival of cancer stem cells, and resistance to chemo/radiotherapy. We postulate that restoring the balance of miRNAs will correct this dysregulation via the direct and simultaneous modulation of downstream stem cell pathways involved in cancer stem cell self-renewal and/or differentiation. The resultant restoration of key regulatory pathways could improve therapeutic response. Restoring tumor suppressor miRNAs and/or inhibiting oncogenic miRNAs may provide a novel molecular therapy for human cancers, potentially via modulating cancer stem cells.

CSC news roundup 2010-04-11

2010-04-11T13:16:00.003-04:00

Cancer Stem Cells: Back to Darwin? (review) [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/csTyxT

Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma [FriendFeed entry][PubMed citation] http://bit.ly/bwUz7C

The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation [FriendFeed entry][News release][PubMed citation] http://bit.ly/cCjVZL

Hedgehog Signaling and Cancer Stem Cells in Hematopoietic Cell Malignancies (USPTO Application) [FriendFeed entry] http://bit.ly/bSbbTF

(WO2010037134) Multi-stage stem cell carcinogenesis [FriendFeed entry][WIPO entry] http://bit.ly/cnksOu

(WO2010037041) Frizzled-binding agents and uses thereof (to target CSC ) [FriendFeed entry] http://bit.ly/aaSJNI

Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer (review) [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/cEcBrJ

Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/cvoGt1

Emerging strategies for the identification and targeting of cancer stem cells (review) [FriendFeed entry][PubMed citation] http://bit.ly/bGOGfd

Stem cells in human breast cancer (OA review) [FriendFeed entry][ResearchGATE entry][PubMed citation] http://bit.ly/aF9E8U

Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signalling [FriendFeed entry][PubMed citation] http://bit.ly/92VkLU

Hypoxia inducible factors in cancer stem cells (minireview) [FriendFeed entry][PubMed citation] http://bit.ly/bGBdxN

Classic view of cancer challenged by new theory (about the CSC model) [FriendFeed entry] http://bit.ly/decqFe

New hope in the horizon: cancer stems cells (OA review) [FriendFeed entry][PubGet entry][Full text PDF] http://bit.ly/9HLmV0

CFI practices called “world’s best’’

2010-04-02T18:41:00.005-04:00

The Canada Foundation for Innovation (CFI) is one of the Canadian funding agencies that is a Member of the Cancer Stem Cell Consortium (CSCC). According to a news release from the CFI, dated March 24, 2010, CFI’s Funding Agreement with the Government of Canada required an overall performance evaluation and value-for-money audit (OPEA). Excerpt from the news release: "KPMG conducted an overall performance evaluation and value-for-money audit of the CFI and an international panel of seven experts in global research and research funding reviewed the findings and produced an independent report".

The news release is entitled: Canada Foundation for Innovation practices called “world’s best’’. The full OPEA, performed by KPMG in 2009, as well as the International Review Panel Report, are available via: OPEA Reports and Summary.

CSC news roundup 2010-03-27

2010-03-27T19:18:00.003-04:00

The Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/cfLPyK

Expansion of CD133+ colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9NLTZ8

Loss of heterozygosity of the tumor suppressor gene Tg737 in the side population cells of hepatocellular carcinomas is associated with poor prognosis [FriendFeed entry][PubMed citation] http://bit.ly/dCQGYL

Cancer Stem Cells: The Final Frontier for Glioma Virotherapy [FriendFeed entry][CiteULike entry][PubMed citation] http://bit.ly/c8GeYb

MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies [FriendFeed entry][ResearchGATE entry][Connotea bookmark][PubMed citation] http://bit.ly/cvcfX7

Expression of Pluripotent Stem Cell Reprogramming Factors by Prostate Tumor Initiating Cells [FriendFeed entry][PubMed citation] http://bit.ly/9jtqLK

Molecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cells [FriendFeed entry] [ResearchGATE entry][PubMed citation] http://bit.ly/9xWial

Cancer stemness and metastasis: Therapeutic consequences and perspectives [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9s0W14

Gene-expression profiles, tumor microenvironment, and cancer stem cells in breast cancer: Latest advances towards an integrated approach [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/dgqE0n

Molecular biology of breast cancer stem cells: Potential clinical applications [FriendFeed entry][PubMed citation] http://bit.ly/as3m3j

In Situ Identification of Putative Cancer Stem Cells by Multiplexing ALDH1, CD44, and Cytokeratin Identifies Breast Cancer Patients with Poor Prognosis [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9rXuWC

c-Jun Induces Mammary Epithelial Cellular Invasion and Breast Cancer Stem Cell Expansion [FriendFeed entry][PubMed citation] http://bit.ly/aInNB2

The Utility and Limitations of Neurosphere Assay, CD133 Immunophenotyping and Side Population Assay in Glioma Stem Cell Research [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9O4PtL

Methods of assaying sensitivity of cancer stem cells to therapeutic modalities (USPTO Application) [FriendFeed entry][FreshPatents entry] http://bit.ly/dcWhtJ

Cancer Stem Cells [Book and Media Reviews] JAMA 2010(Mar 17);303(11):1098 [FriendFeed entry][Book contents] http://bit.ly/9PY8xP

Challenges in the development of future treatments for breast cancer stem cells (OA review) [FriendFeed entry] http://bit.ly/9DGutB

CSC news roundup 2010-03-16

2010-03-15T20:45:00.005-04:00

microRNA-34a is tumor suppressive in brain tumors and glioma stem cells [FriendFeed entry][CSC News post][PubMed citation] http://bit.ly/a5onzu

Enrichment for breast cancer cells with stem/progenitor properties by differential adhesion [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/ceskEY

miR-29a initiates AML by converting myeloid progenitors into self-renewing leukemia SC? [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9sM8Mw

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus [FriendFeed entry][PubMed citation] http://bit.ly/c0SRla

@sciclips MicroRNA as a target for the inhibition of glioblastoma stem cells [FriendFeed entry] http://bit.ly/cvXSwu

@sciclips The most complete systems biology study of cancer stem cell (CSC) differentiation to date [FriendFeed entry][PubMed citation] http://bit.ly/cBe4D3

Presentations on Geron’s Telomerase Inhibitor At AACR Special Conference (Business Wire) [FriendFeed entry] http://bit.ly/cFmyWp

CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9ZmKqT

Targeting leukemia stem cells (by inducing them to divide) [FriendFeed entry][CiteULike entry][PubMed citation] http://bit.ly/aVquQk

RT @cancer_news: [Reflection and Reaction] HER2 as a cancer stem-cell target [FriendFeed entry][PubMed citation] http://is.gd/9udQM

Evidence for self-renewing lung CSCs & their implications [FriendFeed entry][Connotea bookmark][ResearchGATE entry][PubMed citation] http://bit.ly/cje8cc

Cancer as a reprogramming-like disease: Implications in tumor development and treatment [Connotea bookmark][PubMed citation] http://bit.ly/csHdxT

RT: @cancer_news Identification of the cell lineage at the origin of basal cell carcinoma [FriendFeed entry][PubMed citation] http://is.gd/9sT10

Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma [FriendFeed entry][CiteULike entry][PubMed citation] http://bit.ly/bp6dnS

Efficacious Immune Therapy in CML Recognizes Antigens That Are Expressed on CML Progenitor Cells [FriendFeed entry][PubMed citation] http://bit.ly/briNv0

Notch-Blocking Drugs Kill Brain Cancer Stem Cells http://bit.ly/bQqs4f about [PubMed citation] http://bit.ly/cJZ5e3

Universal cancer vaccine containing cancer stem cells [FriendFeed entry] http://bit.ly/bDn5R8

Dock-and-lock (DNL) anti-cancer vaccine for multiple myeloma cancer stem cells [FriendFeed entry] http://bit.ly/csGN8N

Conditioned medium induces generation of side population cells

2010-03-14T09:22:00.003-04:00

Pluripotency-associated genes in human nasopharyngeal carcinoma CNE-2 cells are reactivated by a unique epigenetic sub-microenvironment by Jun-Xia Cao and 8 co-authors, including Quentin Liu, BMC Cancer 2010(Feb 25); 10: 68 [PubMed citation][Full text via PMC][Full text from journal (via Libre OA)]. Conclusion section of the Abstract:

To our knowledge, this is the first study to demonstrate that non-SP single-clone cells can be induced to generate a SP phenotype when they are cultured with conditioned medium of macrophage-like cells, which is associated with the reactivation of pluripotency-associated genes.

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

2010-03-13T15:39:00.003-05:00

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.

CSC news roundup 2010-02-28

2010-02-28T15:02:00.006-05:00

Tumor initiation via loss of cell contact inhibition versus Ras mutation: Do all roads lead to EMT? [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/bIYZjW

CD133+ cells are more resistant to anticancer drugs than CD133- cells in neuroblastoma cell lines [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/bCJKkI

Breast cancer chemoresistance: Emerging importance of CSC [FriendFeed entry][ResearchGATE entry][PubMed citation] http://bit.ly/cmgfj4

Neoplastic stem cells: Current concepts and clinical perspectives [Connotea bookmark][PubMed citation] http://bit.ly/9cRlm2

Nature Methods: Renaissance of classical pathology? Autofluorescence helps identify CSC in glioma [FriendFeed entry][Connotea bookmark][PubMed citation] http://ow.ly/1ag7d

New tool illuminates connections between stem cells and cancer [FriendFeed entry] http://bit.ly/9GLmQC

ALDH Associated With Worse Overall Survival in Patients With Pancreatic Adenocarcinoma [FriendFeed entry][News release][PubMed citation] http://bit.ly/982S5B

ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/clJSiU

Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/9A2kHC

Radiation Resistance of CSC - The 4R's of Radiobiology Revisited [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/ddLt3N

Evaluation of the frequency of putative prostate CSC in primary and metastatic prostate cancer [FriendFeed entry][PubMed citation] http://bit.ly/dba5IN

Immunobiological Characterization of CSC Isolated from Glioblastoma Patients [FriendFeed entry][PubMed citation] http://bit.ly/9t2ReY

Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer [PubMed citation] http://bit.ly/d17EGn

Side population and cancer stem cells: therapeutic implications [PubMed citation] http://bit.ly/ceNr2Y

PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice [FriendFeed entry][CiteULike entry][PubMed citation] http://bit.ly/c9VQTa

Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications [PubMed citation] http://bit.ly/agqb1E

Targeting Cancer Stem Cells: Therapeutic Strategies and Pipeline Developments (Content, Jan 2010) [FriendFeed entry][BioPortfolio] http://bit.ly/cZzr3R

Short (<2 min) video about researching pancreatic CSC at UCLA [FriendFeed entry] http://ow.ly/16NCQ

Lecture: Max Wicha – The CSC hypothesis: biological and clinical implications (57 min) [FriendFeed entry] http://bit.ly/dhKdGD

Targeting A20 Decreases Glioma SC Survival and Tumor Growth

2010-02-23T15:49:00.001-05:00

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.

Progression of primary tumours and metastases

2010-02-21T15:20:00.007-05:00

Parallel progression of tumour and metastases by Serge Koscielny and Maurice Tubiana, Nat Rev Cancer 2010(Feb); 10(2): 156 [PubMed citation]. Commentary on an opinion article: Parallel progression of primary tumours and metastases by Christoph Klein, Nat Rev Cancer 2009(Apr); 9(4): 302-12 [PubMed citation]. An excerpt from the full text of the commentary:

[Data are presented that] are consistent with the linear progression model when it is assumed that there are two types of cells in tumours: those that can initiate metastases (metastasis-forming cells (MFCs)), which probably derive from tumour stem cells[ref 7] and those that probably cannot initiate metastasis because their proliferative ability is limited[refs 7,8,9].

Response to the commentary: Tumour cell dissemination and growth of metastasis by Christoph A Klein, Nat Rev Cancer 2010(Feb); 10(2): 156. Excerpt from the full text of the response:

Finally, the authors declare that the parallel progression model is incompatible with the cancer stem cell hypothesis. As defined above, parallel progression does not address this issue.

The 'linear progression model' described by Christoph Klein "places major evolutionary events in the primary tumour and late dissemination of fully malignant cells that subsequently grow to manifest metastases". In the 'parallel progression model', there is "early dissemination of tumour cells from the primary tumour and ectopic selective adaptation (which is associated with the emergence of genomes fully able to form metastases)" (see Christoph Klein's response).

CSC news roundup 2010-02-13

2010-02-13T15:45:00.014-05:00

ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients [FriendFeed entry][Connotea bookmark][PubMed citation][Full text PDF] http://bit.ly/94fqTs

Good cells gone bad: the cellular origins of cancer [Connotea bookmark][PubMed citation] http://bit.ly/crHb0Y

Targeted Cancer Stem Cell Therapies Start with Proper Identification of the Target - Letter [Connotea bookmark][PubMed citation] and Response [Connotea bookmark][PubMed citation]

Transcriptional Profiles of CD133+ and CD133- Glioblastoma-Derived Cancer Stem Cell Lines Suggest Different Cells of Origin [Connotea bookmark][PubMed citation] http://bit.ly/b255Ec

ALDH1A1(+) cell population enriched in tumor-initiating cells, associated with progression of bladder cancer [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/bDj1yx

Association of stem cell marker CD133 expression with dissemination of glioblastomas [Sciencia entry][Connotea bookmark][PubMed citation] http://bit.ly/b3azCE

NO signaling in perivascular niche promotes stem-like characteristics in glioma cells [FriendFeed entry][PubMed citation] http://bit.ly/c8Enie

TGF-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/bivZQu

Selective targeting of radiation-resistant tumor-initiating cells [FriendFeed entry][Connotea bookmark][PubMed citation] http://bit.ly/chw0Fi

CSC from colorectal cancer-derived cell lines [FriendFeed entry][News release][PubMed citation] http://bit.ly/bDxxnM

Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia SC [FriendFeed entry][News release] http://bit.ly/9g8yUJ

Heterogeneity for Stem Cell-Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer [Connotea bookmark][PubMed citation] http://bit.ly/aVE3SF

Hypothesis: co-existing active-quiescent pools of CSC sub-populations? [FriendFeed entry][PubMed citation] http://bit.ly/acMHpi

Disarming Specialized SC Might Combat Deadly Ovarian Cancer [FriendFeed entry][PubMed citation] http://bit.ly/cTpNTM

A seminal finding for prostate cancer? [Article summary][Topsy entry][PubMed citation] http://bit.ly/7jCq2n

Dissecting Cancer Stem Cell Theories [FriendFeed entry] http://bit.ly/9oilZA

Review about retroviral-induced leukemogenesis and the CSC hypothesis

2010-02-07T14:08:00.001-05:00

Hematopoietic stem cells and retroviral infection by Prabal Banerjee, Lindsey Crawford, Elizabeth Samuelson and Gerold Feuer, Retrovirology 2010(Feb 4); 7(1): 8 [Epub ahead of print][Connotea bookmark][[FriendFeed entry][PubMed Citation][Full text (PDF)].

Includes sections on Leukemia Stem Cells/Cancer Stem Cells (LSC/CSC) and on The Cancer Stem Cell Hypothesis.

CSC news roundup 2010-01-31

2010-01-31T19:45:00.002-05:00

Hypoxia inducible factors in CSC [FriendFeed entry] [Connotea bookmark]

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer [FriendFeed entry] http://is.gd/73pVk

Evidence for self-renewing lung cancer stem cells and their implications [FriendFeed entry] [Connotea bookmark]

The elaboration of a critical framework for understanding cancer: the CSC hypothesis [FriendFeed entry][Connotea bookmark]

IMUC’s ICT-107 vaccine product candidate targets CSC [FriendFeed entry] http://bit.ly/5BnV5q

Putative CSC markers show strong prognostic significance in colorectal cancer [FriendFeed entry][Connotea bookmark] http://bit.ly/7uUuOZ

Cell of Origin Identified for Common Type of Breast Cancer [FriendFeed entry] http://bit.ly/4B0GOl http://bit.ly/5n9Icz

Cancer Biomarker Chase Accelerates [FriendFeed entry] http://bit.ly/57iVWN

CSC suppress immune response against brain tumor [FriendFeed entry] http://bit.ly/6HgW1g

About a new report: Targeting CSC: Therapeutic Strategies and Pipeline Developments [FriendFeed entry] http://bit.ly/8mfqET

More evidence that tumours, like healthy organs, grow from SC. The Economist, 14 Jan 2010 [FriendFeed entry] http://bit.ly/4AeekG

AC133 Epitope, but not the CD133 Protein, Is Lost upon CSC differentiation [FriendFeed entry] http://bit.ly/6r2aGh

Nanosystems capture and destroy circulating tumor cells (CTC) [FriendFeed entry] http://bit.ly/7ebzXI

Evidence that CSC escape and down-regulate host antitumor immunity [FriendFeed entry] http://bit.ly/5vWN8n http://bit.ly/5wgRBV

Stem cells linked to an aggressive cancer of childhood [FriendFeed entry] http://bit.ly/73ldYl http://bit.ly/6YaniV

Role for the SCF-c-kit signaling axis in self-renewal and proliferation of human lung CSC [FriendFeed entry] http://bit.ly/6PxEyW

High-throughput screening of tumor-initiating cells in zebrafish [FriendFeed entry] http://bit.ly/6G06No

The Telomerase Antagonist, Imetelstat, Efficiently Targets Glioblastoma Tumor-Initiating Cells [FriendFeed entry] http://icio.us/t0td2z

OncoMed, Fluidigm to Analyze Tumor Cell Populations [FriendFeed entry] http://bit.ly/7GnYvm

Therapy which fails to target CSC can actually promote malignant features in the recurring tumor! [FriendFeed entry] http://bit.ly/6h7jOp

CXCR1 blockade selectively targets human breast CSC in vitro and in xenografts [FriendFeed entry] http://bit.ly/69ynfK

Analyzing tumors as ecosystems

2010-01-31T14:35:00.003-05:00

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype by So Yeon Park and 4 co-authors, including Kornelia Polyak, J Clin Invest 2010(Jan 25) [Epub ahead of print][FriendFeed entry][Connotea bookmark][Full text is publicly accessible (via Gratis OA)]. PubMed Abstract:

Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.

The final sentence of the Discussion section of the full text:

In summary, in this study we have demonstrated the power of analyzing tumors as ecosystems and suggest that quantitative measures of intratumor diversity might be clinically useful biomarkers predicting prognosis and response to treatment.

Another recent article from the same group: Heterogeneity for Stem Cell–Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer by So Yeon Park and 5 co-authors, including Kornelia Polyak, Clin Cancer Res 2010; 16(3): 876–87 [Epub 2010(Jan 26)][FriendFeed entry][Connotea bookmark][PubMed Citation].

From the Conclusions section of the abstract:

Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage.

Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic SC

2010-01-27T18:51:00.003-05:00

Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells by E Camilla Forsberg and 6 co-authors, including Irving L Weissman, PLoS One 2010(Jan 20);5(1):e8785. [Connotea bookmark][FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.

CSC suppress immune response against brain tumor

2010-01-25T19:04:00.002-05:00

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.

CSC news roundup 2010-01-16

2010-01-16T19:22:00.003-05:00

Medium and Device for Proliferation of Stem Cells and Treatment of Cancer-Related Stem Cell with Resveratrol, United States Patent Application 20100010099. Via FreePatentsOnline.com. Publication Date: January 14, 2010. Assignees: Taipei Veterans General Hospital. [Patentdocs entry].

Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content by Salvatore Pece and 9 co-authors, including Pier Paolo Di Fiore, Cell 2010(Jan 8); 140(1): 62-73. [Connotea bookmark][FriendFeed entry].

Regulating Cancer Stem Cells the miR Way by Marcus E Peter, Cell Stem Cell 2010(Jan 8); 6(1): 4-6. [Commentary on Nat Cell Biol 2009(Dec);11(12):1487-95].

BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells by Mirle Schemionek and 16 co-authors, including Steffen Koschmieder, Blood 2010(Jan 6) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Blocking inflammation receptor kills breast cancer stem cells, study finds, News Release, University of Michigan Health System, January 4, 2010. [About: J Clin Invest doi:10.1172/JCI39397][FriendFeed entry][Another FriendFeed entry].

Geron Announces Publication of Data on Its Telomerase Inhibitor in Glioblastoma, Business Wire, January 4, 2010. [About: Clin Cancer Res 2010(Jan 1);16(1):154-63][FriendFeed entry].

Primary brain tumors, neural stem cell, and brain tumor cancer cells: Where is the link? By Isabelle Germano, Victoria Swiss and Patrizia Casaccia, Neuropharmacology 2010(Jan 1) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity by Andrea Sottoriva, Joost JC Verhoeff and 6 co-authors, Cancer Res 2010(Jan 1); 70(1): 46-56. [PubMed Citation][FriendFeed entry][ResearchGATE entry].

The therapeutic promise of the cancer stem cell concept by Natasha Y Frank, Tobias Schatton and Markus H Frank. Review in J Clin Invest 2010(Jan); 120(1): 41-50. [PubMed Citation][ResearchGATE entry].

Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment, Breast Cancer Res Treat 2009(Nov 13) [Epub ahead of print][PubMed Citation][MDLinx Oncology Summary][FriendFeed entry].

US Patent 7632678 about CSC

2010-01-05T20:04:00.004-05:00

Cancer stem cells and uses thereof, United States Patent 7632678. Issued on December 15, 2009. (Filing Date was November 22, 2006).

Inventors: Loen M Hansford, Kristen M Smith, Alessandro Datti, Freda M Miller and David R Kaplan (Toronto, Canada).

Assignee: The Hospital for Sick Children (Toronto, Ontario, Canada).

Abstract:

Disclosed are enriched preparations of neuroblastoma tumor initiating cells (NB TICs). The NB TICs are capable of self-renewal, initiating neuroblastoma tumor growth in vivo and are capable of being passaged in high frequency. These NB TICs have chromosomal abnormalities and are capable of giving rise to secondary tumor spheres. Methods are also disclosed for preparing the enriched preparations of NB TICs, such as from neuroblastoma tumor tissue and metastasized bone marrow. Also disclosed are methods of screening candidate substances to identify therapeutic agents for the treatment of neuroblastoma. Methods are also provided for screening a sample for neuroblastoma, as well as for screening a sample to identify the stage of neuroblastoma present. Kits are also provided for selecting appropriate anti-neuroblastoma compounds for a patient, and utilize isolated compositions of the patients' neuroblastoma tumor initiating cells. In this manner, a customized medicinal profile for the patient may be devised.

CSC news roundup 2010-01-03

2010-01-03T15:05:00.007-05:00

Glioma stem cell research for the development of immunotherapy, Neurosurg Clin N Am 2010(Jan); 21(1): 159-66 [PubMed Citation][Connotea bookmark].

Cancer stem cell and niche, Front Biosci (Schol Ed) 2010(Jan 1); 2: 184-93 [PubMed Citation][FriendFeed entry][Connotea bookmark].

Cancer stem cell niche as a therapeutic target by Alexey Bersenev, Hematopoiesis, December 27, 2009 [FriendFeed entry].

Leukemia Stem Cells, Semin Cancer Biol 2009(Dec 22) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Aldehyde Dehydrogenase 1–Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer, Clin Cancer Res 2009(Dec 22) [Epub ahead of print][PubMed Citation][FriendFeed entry][Connotea bookmark].

Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers, PLoS ONE 2009(Dec 21); 4(12): e8377 [PubMed Citation][Full text via PMC][ResearchGATE entry][Connotea bookmark].

Are cancer stem cells concentrated in more alkaline hypoxic regions of tumors? Med Hypotheses 2009(Dec 16)[Epub ahead of print][PubMed Citation].

Targeted therapy in haematological malignancies, J Pathol 2009(Dec 10) [Epub ahead of print][PubMed Citation][ResearchGATE entry][Connotea bookmark].

Video of Robert Weinberg interviewed about Breast Cancer Stem Cells & the EMT, SABCS 2009 Interview, American Association for Cancer Research, December 10, 2009 [FriendFeed entry].

Professor Dick Honored For Making Sense of Cancer Stem Cells by Mikkael A Sekeres, ASH News Daily, December 8, 2009 [FriendFeed entry].

Spices halt growth of breast stem cells, study finds, PhysOrg.com, December 7, 2009 [FriendFeed entry].

Aging, inflammation and cancer

2009-12-30T12:04:00.003-05:00

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

2009-12-24T08:28:00.017-05:00

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

2009-12-12T08:28:00.003-05:00

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

2009-12-09T14:51:00.003-05:00

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

2009-12-06T14:50:00.006-05:00

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

2009-12-05T11:28:00.003-05:00

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

2009-12-03T19:59:00.005-05:00

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.

CSC news roundup 2009-11-26

2009-11-26T08:26:00.003-05:00

Distinct population of highly malignant cells in a head and neck squamous cell carcinoma cell line established by xenograft model, 7thSpace Interactive, November 16, 2009 [J Biomed Sci 2009(Nov 16);16(1):100 (OA)][PubMed Citation][FriendFeed entry].

Tumor-initiating Cells Detected in Pten Null Prostate Cancer Model, PhysOrg.com, November 12, 2009 [Cancer Res 2009(Nov 15); 69(22):8555-62][PubMed Citation][FriendFeed entry].

Mouse Models for Cancer Stem Cell Research by Le Cheng and 4 co-authors, including Alexander Y Nikitin, Toxicol Pathol 2009(Nov 17) [Epub ahead of print][PubMed Citation].

Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment by Erika Resetkova and 6 co-authors, including Sunil Badve, Breast Cancer Res Treat 2009(Nov 13) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Recognition and Killing of Brain Tumor Stem-Like Initiating Cells by CD8+ Cytolytic T Cells by Christine E Brown and 10 co-authors, including Michael C Jensen, Cancer Res 2009(Nov 10) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Notch Pathway Blockade Depletes CD133-Positive Glioblastoma Cells and Inhibits Growth of Tumor Neurospheres and Xenografts by Xing Fan and 14 co-authors, including Charles G Eberhart, Stem Cells 2009(Nov 10) [Epub ahead of print][PubMed Citation][Connotea bookmark].

Targeting breast stem cells with the cancer preventive compounds curcumin and piperine by Madhuri Kakarala and 8 co-authors, including Max S Wicha, Breast Cancer Res Treat 2009(Nov 7) [Epub ahead of print][PubMed Citation].

Identification of single chain antibodies to breast cancer stem cells using phage display by Deniz Gur and 5 co-authors, including Max S Wicha and David N Krag, Biotechnology Prog 2009(Nov 6) [Epub ahead of print][PubMed Citation].

Methodologies in assaying prostate cancer stem cells by Hangwen Li and 7 co-authors, including Dean G Tang, Methods Mol Biol 2009; 568: 85-138 [PubMed Citation].

Pituitary adenoma stem cells by Patrizia Tunici and John S Yu, Methods Mol Biol 2009; 568: 195-201 [PubMed Citation].

Targeting breast cancer stem cells by Max S Wicha, The Breast 2009(Oct); 18(Suppl 3): S56-8.

IMUC letter to shareholders

2009-11-21T08:02:00.004-05:00

ImmunoCellular Therapeutics Issues Letter to Shareholders, News Release, ImmunoCellular Therapeutics (IMUC), November 19, 2009. Excerpt:

Signed key manufacturing agreement. The Company entered into an agreement with Formatech, Inc. for the manufacture of IMUC's cancer stem cell vaccine product candidate, ICT-121, the Company's lead product candidate that targets cancer stem cells and may have applicability to multiple types of cancer, for an upcoming clinical trial. The Phase I clinical trial of ICT-121, will target glioblastoma (brain cancer) and is expected to begin early next year, pending clearance by the FDA. ICT-121 is an "off-the-shelf" product, and this agreement calls for Formatech to prepare the vials of cancer vaccine for the clinical trial under a GMP (Good Manufacturing Practices) environment.

For a previous news release about this agreement, see: ImmunoCellular Therapeutics Signs Manufacturing Agreement with Formatech for Clinical Trial of ICT-121 Immunotherapy, June 24, 2009 [Formatech release][IMUC release].

Targeting of AML-leukemic SC with monoclonal antibodies

2009-11-19T20:54:00.002-05:00

Targeting of AML-leukemic stem cells with monoclonal antibodies by Erwin M Lee‌ and Richard B Lock, Future Oncol 2009(Nov); 5(9): 1327-30 [PubMed Citation][FriendFeed entry][Full text PDF]. Final sentence of the full text of this Editorial:

An AML patient surface immunophenotype is relatively cost-effective to characterize, raising the prospect of individualized therapy based on a selection of available MAbs. Most certainly, we are entering a new and exciting era in the struggle to improve outcome in adult AML.

CSC news roundup 2009-11-10

2009-11-10T20:10:00.005-05:00

The cancer stem cell microenvironment and anti-cancer therapy by Veerander P S Ghotra, Jordi C Puigvert and Erik H J Danen. Review in Int J Radiat Biol 2009(Nov); 85(11): 955-62 [PubMed Citation].

Cancer Stem Cells : A Reality, A Myth, A Fuzzy Concept or A Misnomer? An Analysis by Carine Maenhaut, Jacques E Dumont, Pierre Roger and Wilma C G van Staveren. Review in Carcinogenesis 2009(Oct 25) [Epub ahead of print][PubMed Citation].

Colorectal cancer stem cells by Paul Salama and Cameron Platell, Review in ANZ J Surg 2009(Oct); 79(10): 697-702 [PubMed Citation][FriendFeed entry].

Identification and targeting of cancer stem cells by Tobias Schatton, Natasha Y Frank and Markus H Frank. Review in Bioessays 2009(Oct); 31(10): 1038-49 [PubMed Citation].

Cancer stem cells: Symmetry is key by Mhairi Skinner, Nature Reviews Cancer 2009; 9: 768-9. A commentary about [Cell 2009 Sep 18;138(6):1083-95][FriendFeed entry].

On cancer stem cells (for the lay public) [All Things Stem Cell 2009(Oct 31)] by Teisha Rowland [FriendFeed entry].

Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells. [Cancer Res 2009(Oct 15);69(20):8058-66][PubMed Citation][FriendFeed entry].

CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer by Michael D Curley and 10 co-authors, including Bo R Rueda and Rosemary Foster. Stem Cells 2009(Oct 8) [Epub ahead of print][PubMed Citation].

Heterogeneity in the AML stem cell pool

2009-11-07T10:57:00.003-05:00

Heterogeneity in the AML stem cell pool by Laura E Hays, Blood 2009(Nov 5); 114(19): 3976-7 [PubMed Citation][FriendFeed entry]. Excerpt:

To examine AML and stem cell diversity, Heuser and colleagues develop a novel murine model that closely mimics aggressive human AML and demonstrate an essential role of Stat5 in leukemic stem cell renewal.

Comment on: Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal by Michael Heuser and 14 co-authors, including Gerald Krystal and R Keith Humphries, Blood 2009(Nov 5); 114(19): 3983-93 [Epub 2009(Aug 10)][PubMed Citation].

Featured Article in Cell Stem Cell (Nov 09)

2009-11-05T19:13:00.006-05:00

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].

CSC news roundup: 2009-11-02

2009-11-02T20:08:00.005-05:00

Compositions and Methods for Determining Cancer Stem Cell Self-Renewal Potential, University of California, San Diego Technology Transfer Office, November 2, 2009. [SD2009-192][Tech ID: 19976].

ImmunoCellular's Promising Brain Cancer Vaccine, Mike Havrilla, Seeking Alpha, October 28, 2009. [Reuters News Release].

MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications, Jeffrey T DeSano and Liang Xu, AAPS J 2009(Oct 20). [PubMed Citation].

Sphere and/or xenograft formation may be useful to survey colitic patients at risk of developing cancer? [Cancer Res 2009 (Oct 15);69(20):8208-15][PubMed Citation][News Release].

Recent studies regarding stem cell origin of various solid tumors are discussed briefly in this review. [Onkologie 2009 (Oct);32(10):605-9][PubMed Citation].

Squelching glioblastoma stem cells by targeting REST for proteasomal degradation by Peisu Zhang and 4 co-authors, including Jeremy N Rich and Mark P Mattson, Trends Neurosci 2009(Nov);32(11):559-65 [Epub 2009(Sep 11)][PubMed Citation].

Methylation dosage effect controls stem cell function in leukemia. [Nat Genet 2009 (Nov);41(11):1207-15][PubMed Citation][News Release].

Disease Team awards announced

2009-10-29T08:50:00.007-04:00

Novel funding mechanism speeds the path of research, News Release, California Institute for Regenerative Medicine (CIRM), October 28, 2009. Excerpt:

The California Institute for Regenerative Medicine, the state stem cell agency, and two international partners awarded more than $250 million to 14 multidisciplinary teams of researchers in California, the UK and Canada to develop stem cell-based therapies for 11 diseases. The Disease Team Research Awards include approximately $8 million from the Medical Research Council, UK, and approximately $35 million from the Cancer Stem Cell Consortium, Canada, to fund the international portions of the collaborations.

CSC targeted to prevent relapse

2009-10-25T09:10:00.005-04:00

Cancer stem cells targeted to prevent relapse by Vivek Sinanan, The Johns Hopkins News-Letter, October 26, 2009. In part, the news item appears to be based on this editorial: Controversies in cancer stem cells by Richard J Jones, J Mol Med 2009(Oct 23) [Epub ahead of print][PubMed Citation][Full text]. In turn, the editorial cites these articles, which will be published in J Mol Med 2009; 87(11):

Cancer stem cells: controversies in multiple myeloma, Sarah K Brennan, William Matsui, J Mol Med 2009(Sep 17) [Epub ahead of print][PubMed Citation].

Brain cancer stem cells, Sara GM Piccirillo and 4 co-authors, including Khalid Shah, J Mol Med 2009(Sep 29) [Epub ahead of print][PubMed Citation].

Colon cancer stem cells, Lucia Ricci-Vitiani and 4 co-authors, including Ruggero De Maria, J Mol Med 2009(Sep 2) [Epub ahead of print][PubMed Citation].

Cancer stem cells-clinical relevance, Richard J Jones, J Mol Med 2009(Oct 10) [Epub ahead of print][PubMed Citation].

Eleven likely winners of Disease Team awards

2009-10-23T20:12:00.006-04:00

Results will soon be announced for the Disease Team Research Awards Competition of the California Institute for Regenerative Medicine (CIRM). These awards will support multi-disciplinary teams of scientists in pursuit of therapies for specific diseases. See: The Lucky 11 and $167 Million in Stem Cell Research Cash, David Jensen, California Stem Cell Report, October 23, 2009. First two paragraphs:

The California stem cell agency has pinpointed 11 likely winners of grants and loans up to $20 million each in the agency's ambitious disease team round, which was once projected at $210 million.

The awards are scheduled to be formally approved next week by the CIRM board of directors at a two-day meeting in Los Angeles at the Luxe Hotel. CIRM's Grants Working Group decided earlier that 11 proposals merited funding. The CIRM board almost never rejects a recommendation for funding by its reviewers.

Comment: Participation in the Disease Team Research Awards program is the first initiative launched by the Cancer Stem Cell Consortium (CSCC), in collaboration with CIRM. This is an international collaboration to advance cancer stem cell research, involving both Canadian and Californian scientists. See this previous post: CIRM/CSCC Joint Announcement: Disease Teams Awards, October 23, 2008.

Targeting cancer stem cells

2009-10-17T18:08:00.007-04:00

Griffin Securities Announces Investment Opinion on Targeting Cancer Stem Cells, Yahoo Finance, October 9, 2008. First paragraph:

Griffin Securities (“Griffin”), a research-driven investment banking firm, has released an industry report on the subject of targeting cancer stem cells (CSCs). The stem cell hypothesis offers a rational approach to preventing, diagnosing, and treating malignant growth. Covered in the report are five classes of drugs nearing the Phase II clinical trial that provides human proof-of concept data, a crucial stage of development: Notch signaling, PI3k/akt pathway, immunotherapeutics, molecular chaperons, and hedgehog signaling.

See also: Firms Seek to Prove Cancer Stem Cell Hypothesis by Keith A Markey (scientific director at Griffin Securities), Genetic Engineering & Biotechnology News, Oct 15, 2009 (Vol 29, No 18).

Comments: Information can be found online about some of the drugs mentioned in the article by Keith A Markey. Two examples:

Notch signaling: OMP-21M18
A humanized monoclonal antibody directed against the N-terminal epitope of Notch ligand DLL4 (delta-like 4) with potential antineoplastic activity. Anti-DLL4 monoclonal antibody OMP-21M18 binds to the membrane-binding portion of DLL4 and prevents its interaction with Notch-1 and Notch-4 receptors, thereby inhibiting Notch-mediated signaling and gene transcription, which may impede tumor angiogenesis. Activation of Notch receptors by DLL4 stimulates proteolytic cleavage of the Notch intracellular domain (NICD); after cleavage, NICD is translocated into the nucleus and mediates the transcriptional regulation of a variety of genes involved in vascular development. The expression of DLL4 is highly restricted to the vascular endothelium.
One Phase 1 trial of OMP-21M18 [ClinicalTrials.gov Identifier: NCT00744562].

Hedgehog signaling: IPI-926
An orally bioavailable, cyclopamine-derived inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Hedgehog pathway inhibitor IPI-926 binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations. The Hh signaling pathway plays an important role in proliferation of neuronal precursor cells in the developing cerebellum and other tissues.
One Phase 1 trial of IPI-926 [ClinicalTrials.gov Identifier: NCT00761696].

A search of the Canadian Cancer Trials database indicated no trial sites, for either of these two particular trials, that are located in Canada.

Aspirin may affect survival of CSC?

2009-10-12T12:10:00.008-04:00

Aspirin protection for Lynch syndrome, PhysOrg.com, September 28, 2009. Excerpt:

Professor John Burn, from the Institute of Human Genetics at Newcastle University told the congress ECCO 15 - ESMO 34 held in Berlin on September 21 2009, that he believed that he and his colleagues may have uncovered a simple way of controlling cancer stem cells, which are essential to the formation of malignant tumours.

The clinical trial, which involved 1071 carriers of the Lynch syndrome mutation in 42 centres worldwide, randomised participants to a daily dose of 600mg aspirin and/or 30g Novelose, a resistant starch that escapes digestion in the small intestine.

See also a video (00:11:18) of Prof John Burn, who "talks to ecancer editor Prof Gordon McVie about the results of his trial" (posted September 23, 2009).

And, Aspirin protects against colorectal cancer, says international clinical trial, News Release, ECCO 15 – ESMO 34, September 21, 2009. Excerpt:

The mechanism by which aspirin protects against cancer has yet to be elucidated, but the scientists believe that cancer stem cells are involved.

Also, Aspirin taking on colon cancer, Mark Gertskis, Pharmacy News, September 28, 2009.

Comment: A heads-up: Daily dose of aspirin not safe for everyone, Jodi Mailander Farrell, MiamiHerald.com, September 29, 2009.

CSC news roundup: 2009-10-06

2009-10-06T12:28:00.022-04:00

Tumour-initiating cells: challenges and opportunities for anticancer drug discovery by Bin-Bing S Zhou and 5 co-authors, including Peter B Dirks, Nat Rev Drug Discov 2009(Oct); 8(10): 806-23 (Review) [PubMed Citation].

The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype by John M Heddleston and 4 co-authors, including Jeremy N Rich, Cell Cycle 2009(Oct 3); 8(20) [Epub ahead of print][PubMed Citation].

Identification of a myeloid committed progenitor as the cancer initiating cell in acute promyelocytic leukemia by Florence C Guibal and 11 co-authors, including Daniel G Tenen, Blood 2009(Oct 1) [Epub ahead of print][PubMed Citation].

Targeting leukaemia at the roots by Alison Ross, Science Update blog, Cancer Research UK, September 28, 2009.

"Tax-ing" the cancer stem cell by Gerold Feuer, Blood 2009(Sep 24); 114(13): 2568-9 [PubMed Citation].

Cancer stem cell research gains traction, tackles new targets by Katherine Harmon, Scientific American, September 23, 2009 [FriendFeed entry].

A progenitor cell origin of myeloid malignancies by Hiroshi Haeno, Ross L Levine, D Gary Gilliland and Franziska Michor, Proc Natl Acad Sci USA 2009(Sep 29); 106(39): 16616-21 [Epub 2009(Sep 21)][PubMed Citation].

Vitro's Cancer Stem Cell Therapy Complements New Hedge Hog Drugs, News Release, September 10, 2009 [Vitro Biopharma].

Cancer stem cells in breast cancer and metastasis by Jessica C Lawson, Gregory L Blatch and Adrienne L Edkins, Breast Cancer Res Treat 2009(Sep 4) [Epub ahead of print] (Review). [PubMed Citation].

Cancer stem cell genomics: the quest for early markers of malignant progression by Oswaldo K Okamoto, Expert Rev Mol Diagn 2009(Sep); 9(6): 545-54 (Review). [PubMed Citation].

A contrarian view of 'stemness'

2009-10-01T08:27:00.012-04:00

The 'stem cell' concept: is it holding us back? by Arthur D Lander, J Biol 2009(Sep 21); 8(8):70 [Epub ahead of print][Related FriendFeed entry][PubMed Citation][Full text is publicly accessible (via Libre OA)]. Abstract:

Developmental biology, regenerative medicine and cancer biology are increasingly occupied with the molecular characterization of stem cells. Yet recent work adds to a growing body of literature suggesting that 'stemness' cannot be reduced to the molecular features of cell types, and is instead an emergent property of cell lineages under feedback control.

Brief excerpt from the full text: "Like gene or phlogiston, the term 'stem cell' is a scientific concept. Stem cells are very much in the news, thanks to a dramatic upsurge in interest in their therapeutic potential".

Another excerpt from the full text:

For example, in the case of cancers that are stem cell driven, it is not clear that we actually have grounds to assume that the specific chemotherapeutic targeting of cancer stem cells will necessarily stop tumors in their tracks. Indeed, if feedback and lineage progression continue to take place in cancerous tissues, we might observe that, under different conditions - different stages of tumorigensis, different parts of a tumor, different amounts of tumor cells - that different cell types will assume the role of 'cancer stem cell'. The therapeutic implications of this possibility are clearly substantial.

An interview with Arthur Lander is at: Q&A: Is stem cell research misguided? by Bob Grant,TheScientist.com, September 29, 2009 [FriendFeed entry].

Comment: The major contrarian perspective in this opinion piece is the comparison of the stem cell concept with the phlogiston concept. This comparison is discussed further in the Q & A interview. The Comments section of Dr. Lander's article includes an answer to a question that I asked: What about purified stem cells? As part of a discussion on FriendFeed, I also asked: Is the debate about 'stemness' becoming another version of the nature-nurture debate? So far, no response to this question.

Diabetes drug metformin appears to target breast CSC

2009-09-22T19:42:00.005-04:00

Diabetes Drug Metformin Shows Promise as a Breast Cancer Treatment, NCI Cancer Bulletin 2009(Sep 22); 6(18). First two paragraphs:

Low doses of the commonly used diabetes drug metformin may be an effective treatment for breast cancer, primarily because the drug appears to target breast cancer stem cells, Harvard Medical School researchers reported online September 14 in Cancer Research. Cancer stem cells, also called tumor-initiating cells, are thought to be relatively rare cells that can give rise to new tumors and are resistant to standard cancer treatments.

In the study, the combination of metformin and the chemotherapy agent doxorubicin was more effective than either drug alone at eliminating cancer cells and cancer stem cells in cultured cell lines of four genetically distinct breast cancer types, including HER2-positive and triple-negative breast cancers. In a breast cancer mouse model, the drug combination eliminated tumors and prevented regrowth, whereas doxorubicin alone only reduced tumor size and did not prevent regrowth, and metformin alone had little effect.

This bulletin is about the publication: Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission by Heather A Hirsch, Dimitrios Iliopoulos, Philip N Tsichlis and Kevin Struhl, Cancer Res 2009(Sep 14) [Epub ahead of print][PubMed Citation].

Aurothiomalate being studied in a preclinical lung cancer model

2009-09-20T19:28:00.006-04:00

Mayo Clinic researchers find lung cancer oncogene holds key to turning off cancer stem cells, News Release, Mayo Clinic, September 8, 2009. First two paragraphs:

Scientists at the Mayo Clinic campus in Florida have found that the lung cancer oncogene PKCiota is necessary for the proliferation of lung cancer stem cells. These stem cells are rare and powerful master cells that manufacture the other cells that make up lung tumors and are resistant to chemotherapy treatment.

Their study, published in the Oct. 1 issue of Cancer Research, also shows that an agent, aurothiomalate, being tested at Mayo Clinic in a phase I clinical trial substantially inhibits growth of these cancer stem cells.

The news release is about this publication: Atypical Protein Kinase C{iota} Is Required for Bronchioalveolar Stem Cell Expansion and Lung Tumorigenesis by Roderick P Regala and 5 co-authors, including Alan P Fields, Cancer Res 2009(Sep 8) [Epub ahead of print][PubMed Citation]. The final paragraph of the full text:

Our present results show that aurothiomalate exhibits potent antiproliferative activity toward the tumor stem cell niche in a relevant preclinical lung cancer model. Future studies will be required to assess whether aurothiomalate has similar antiproliferative effects on human lung cancer stem cells isolated from primary human lung tumors.

Comment: The publication reports results that were obtained using a mouse model. The News Release states that a Phase I clinical trial is under way at the Mayo Clinic, but this trial isn't mentioned in the full text of the publication in Cancer Research. According to MedicineNet.com, aurothiomalate is a "gold-containing chemical (salt) used in treating rheumatoid arthritis".

IP rules for CIRM disease team project delayed

2009-09-20T08:58:00.001-04:00

Prop. 71 Minutia Stalls CIRM Again, David Jensen, California Stem Cell Report, September 16, 2009. First two paragraphs:

The board of directors of the California stem cell agency Tuesday failed to achieve a quorum and was forced to put off action on regulations tied to its ambitious, $210 million disease team grant round, the largest ever in CIRM history.

That means it will be at least another two weeks or more before the board can act on the IP rules that it needs for disease team project. The grants are scheduled to be awarded later this year

Comment: To see previous posts in this blog about the Disease Teams Awards, see posts with the tag "Disease Teams".

Researchers find new kind of prostate SC in mice

2009-09-15T19:18:00.004-04:00

New Type Of Adult Stem Cells Found In Prostate May Be Involved In Cancer Development, ScienceDaily, September 10, 2009. Excerpts:

The new study may resolve this conundrum because the newly discovered adult stem cells are also luminal cells. "Previous research suggested that prostate cancer originates from basal stem cells, and that during cancer formation these cells differentiate into luminal cells," said Dr. Shen. "Instead, CARNs may represent a luminal origin for prostate cancer" [CARNs stands for "castration-resistant Nkx3.1-expressing cells"].

And indeed, the researchers found that CARNs in mice can give rise to prostate cancers, after the cells lose the activity of PTEN, a gene that is frequently mutated in human prostate cancers.

See also: New Progenitor Cell in Mice Can Cause Prostate Cancer, Michael Smith, Medpage Today, September 9, 2009; Researchers find prostate cancer stem cell, Reuters, September 9, 2009.

These news items are about the publication: A luminal epithelial stem cell that is a cell of origin for prostate cancer by Xi Wang and 9 co-authors, including Michael M Shen, Nature 2009(Sep 9) [Epub ahead of print][PubMed Citation].

Comment: These CSCs were found in mice, and "it is unclear whether CARNs exist in the normal human prostate and if human prostate cancers can originate from these CARNs" (see last paragraph of the Medpage Today article).

Found via: Two Studies Make Promising Advances in Prostate Cancer Research, Denis Cummings, FindingDulcinea, September 10, 2009.

Promising novel lipid molecule for breast cancer?

2009-09-12T15:53:00.014-04:00

New stem cell identification technology could cure breast cancer, Reuters, September 11, 2009. [Twitter entry]. Excerpt:

The key behind GENova's biotechnology is tracing cancer cells to their origin, the very stem cells from where the first malignant cell arose. ...

See also: GENova files patent for new breast cancer treatment, Reuters, September 10, 3009. Excerpt:

... The technology behind Tetanolic acid involved identifying specific characteristics of these cancer stem cells and then tailoring a lipid (Tetanolic acid) that can identify these characteristics and then attack the malignant cells whilst leaving healthy cells intact. This tailor-made cancer treatment strategy is far superior to any existing therapies, as it terminates the cancer at the source, with no side effects, and no harm to surrounding healthy tissues.

From the Pipeline section of the website of GENova Biotherapeutics:

Tetanolic acid: Promising novel lipid molecule for breast cancer

Known as an alpha hydroxyoleic acid, tetanolic acid is a form of a lipid which is also found as a main component of olive oil. Alpha hydroxyoleic acids are able to interact with the cell membrane in order to control its composition or structure with affect on the receptors on the membrane. This control mechanism affects the growth and proliferation of cells – and seeing that cancer is characterised as a normal proliferation of cells, these lipids can potentially prevent cancer spread (Ohba et al., 2007 Int. J. Cancer 121 (1)).

Tests have been shown that such analogues of oleic acid are able to prevent the growth and spread of cancers, including breast cancer, in mice. That is why GENova's Tetanolic acid is a candidate for development of an anti-cancer medicament in humans.

The reference is to: Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26 by Yusuke Ohba and 14 co-authors, including Hiroshi Nojima, Int J Cancer 2007(Jul 1); 121(1): 47-54. [PubMed Citation].

For recent background information, see: Form 10-Q for GENOVA BIOTHERAPEUTICS INC., Yahoo Finance, August 14, 2009. Excerpts:

From inception, Kinder Travel Inc. had been a travel agency offering a full range of travel services including corporate travel, vacations, cruise holidays, and group tours. Since Kinder Travel Inc. was incurring continued losses in the travel industry, the Board of Directors decided it was in the best interests of the Corporation to pursue other business opportunities. Through his past contacts in the bio-medical industry, the then President of Kinder Travel Inc. initiated negotiations with Phoinos Oxford Lifesciences Limited, a company incorporated under the laws of the Federation of St. Kitts & Nevis ("Phoinis Oxford"), for the purchase of medical patents for the treatment of prostate and breast cancers. On April 15, 2009, Kinder Travel Inc. entered into an asset purchase agreement dated April 15, 2009 (the "Asset Purchase Agreement") with Phoinos Oxford.

The Company subsequently changed its to "Genova Biotherapeutics Inc." Our shares of common stock now trade on the Over-the-Counter Bulletin Board under the symbol "GVBP.OB".

For details about the sale of medical patents (filed in Denmark and the United Kingdom) by Phoinos Oxford Lifesciences to Kinder Travel, Inc. (renamed GENova Biotherapeutics Inc.), see: Kinder Travel, Inc. Form PRER14C, June 17, 2009.

A recent clarification: GENova issues clarifying press release, Bloomberg.com, September 12, 2009. Excerpt:

GENova owns the rights to a range of drug targets and has filed patent application for all of them. The patents have not yet been approved and are therefore considered 'patents-pending'. It has been brought to GENova's attention that previous releases were not entirely clear on this issue and may have been misconstrued by some investors.

Comment: A PubMed search and a Google Scholar search didn't yield any additional information about tetanolic acid. A Google search for "tetanolic acid for the treatment of breast cancer" did reveal that NextGen Bioscience Inc. acquired tetanolic acid in November of 2007, but that, while still owning tetanolic acid, was in financial difficulties by February of 2008. This company's website is not online at present. I've not been able to find information online about the transfer of ownership if tetanolic acid from NextGen Bioscience Inc. to Phoinos Oxford Lifesciences Ltd., the seller of tetanolic acid to GENova Biotherapeutics (see above).

A recent publication that may also be relevant is: Pivotal role of dihydrofolate reductase knockdown in the anticancer activity of 2-hydroxyoleic acid by Victoria Lladó and 7 co-authors, including John E Halver and Xavier Busquets, Proc Natl Acad Sci USA 2009(Aug 18); 106(33): 13754-8 [Epub 2009(Aug 3)]. [PubMed Citation][ Full text].

Bidirectional interconvertibility between CSCs and non-CSCs?

2009-09-09T15:38:00.004-04:00

Cancer stem cells: mirage or reality? Piyush B Gupta, Christine L Chaffer and Robert A Weinberg, Nat Med 2009(Sep); 15(9): 1010-1012 [Epub 2009(Sep 4)]. [FriendFeed entry] PubMed Abstract:

The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.

Excerpt from the full text:

Figure 1: Stem-differentiation hierarchy.

[Figure]

Increased plasticity may be present within cancer populations, enabling bidirectional interconvertibility between CSCs and non-CSCs.

Last two sentences of the full text:

However, if non-CSCs can indeed give rise to CSCs, this plasticity would frustrate attempts to cure tumors by eliminating CSCs alone, as therapeutic elimination of CSCs may be followed by their regeneration from residual non-CSCs, allowing tumor regrowth and clinical relapse. We, therefore, suspect that optimal therapeutic regimens will need to incorporate agents that target both CSCs and non-CSCs if truly curative therapies are ever to be achieved.

Comment: This article presents a novel model of the "stem-differentiation hierarchy" involving CSCs and non-CSCs. The model includes the possibility that "a dynamic equilibrium may exist between CSCs and non-CSCs within tumors" that "may be shifted in one direction or another by contextual signals within the tumor microenvironment that influence the probability of interconversion between the CSC and non-CSC compartments ...". It's unfortunate that the article isn't openly accessible. If it were OA (with an appropriate Creative Commons License), a copy of the model depicted in Figure 1 could have been included in this post.

Cancer cell heterogeneity: an essay

2009-09-04T18:59:00.003-04:00

Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution by Mark Shackleton, Elsa Quintana, Eric R Fearon and Sean J Morrison, Cell 2009(Sep 4); 138(5): 822-29. [FriendFeed entry][Full text]. Summary:

The identification and characterization of cancer stem cells might lead to more effective treatments for some cancers by focusing therapy on the most malignant cells. To achieve this goal it will be necessary to determine which cancers follow a cancer stem cell model and which do not, to address technical issues related to tumorigenesis assays, and to test the extent to which cancer cell heterogeneity arises from genetic versus epigenetic differences.

Imatinib refractoriness of leukemia-initiating cells

2009-09-04T11:55:00.004-04:00

Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder by Katherine I Oravecz-Wilson and 11 co-authors, including Sean J Morrison and Theodora S Ross, Cancer Cell 2009(Aug 4); 16(2): 137-48. Last sentence of the PubMed Abstract:

Although imatinib dramatically decreased disease burden, LICs persisted, demonstrating imatinib refractoriness of LICs.

Prom1-expressing cells not essential for gliomagenesis

2009-09-01T18:44:00.002-04:00

Glioblastoma Formation from Cell Population Depleted of Prominin1-Expressing Cells, Elites TV, August 29, 2009. [Twitter entry].

This news item provides the abstract of an article (with the same title) by Kenji Nishide, Yuka Nakatani, Hiroshi Kiyonari and Toru Kondo, published in PLoS One 2009(Aug 31); 4(8): e6869. [PubMed Citation][Full text is publicly accessible (via Libre OA)]. Last sentence of the abstract:

Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

Two publications about colorectal cancer

2009-08-31T19:05:00.009-04:00

The Key to Stopping Colon Cancer? Med Tech Sentinel, August 30, 2009. Excerpt:

Scientists in Switzerland may have found a way to inhibit the growth of colon cancer in humans, says a new study published in EMBO Molecular Medicine. Researchers in Geneva discovered that by blocking a particular biological pathway, they could prevent the growth of tumors, metastatic lesions, and cancer stem cells. The Hedgehog-GL1 (HH-GL1) pathway appears to be crucial in the progression of colon cancer to an incurable, late stage. Cells use HH-GL1 to communicate with each other to determine position, growth and survival.

See also: 'Hedgehog' pathway may hold key to anti-cancer therapy, EurekAlert, August 26, 2009.

These news reports are about the publication: Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion by Frédéric Varnat and 6 co-authors, including Ariel Ruiz i Altaba, EMBO Molecular Medicine 2009(Aug 27) [Epub ahead of print][Abstract][Full text].

Another excerpt from The Key to Stopping Colon Cancer? (Med Tech Sentinel, August 30, 2009):

Earlier this month, scientists in North Carolina found another genetic target that may be useful in treating colorectal cancer. The pseudokinase ERBB3 is closely related to epidermal growth factor receptor (EGFR), which is already a target of several drugs used to treat colorectal cancer. Scientists found that genetically blocking ERBB3 was effective at preventing the disease in mice with colon cancer. In human colon cancer cells, removing ERBB3 caused a dramatic increase in cell death.

About the publication: Tumor-specific apoptosis caused by deletion of the ERBB3 pseudo-kinase in mouse intestinal epithelium by Daekee Lee and 8 co-authors, including David W Threadgill, J Clin Invest 2009(Aug 17) [Epub ahead of print][PubMed Citation][Full text].

Globe & Mail article on CSCs

2009-08-28T20:19:00.007-04:00

Cancer stem cells spur hope, skepticism by Jill Colvin, The Globe and Mail, August 27, 2009. [WebCite cache][Twitter entry][FriendFeed entry]. Excerpt:

Ontario Cancer Institute researcher John Dick, arguably the world's leading authority in the field, first identified stem cells in leukemia in the 1990s. Today, few doubt they play a key role in blood cancers.

In addition to this comment about the crucial contributions of John Dick, research on brain-tumour stem cells by Samuel Weiss is noted. There's also mention of the MIT and Harvard joint venture, Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening, published in Cell 2009(Aug 13). [See also this post in CSC News, August 14, 2009].

The criticisms by Scott Kern (such as: The fuzzy math of solid tumor stem cells: a perspective) of application the CSC hypothesis to colon, breast, or lung cancer are outlined. There's also a comment attributed to Richard Hill:

The hypothesis also hinges on the assumption that these cells are rare. Otherwise, traditional cancer therapies that shrink tumours would be killing them, too, and there would be no need to develop specialized treatments.

The "game-changing paper" by a team led by Sean Morrison, Efficient tumour formation by single human melanoma cells is also discussed. [See another post in CSC News, December 3, 2008, about this paper]. This research supports the view that "... stem cells may be key for some kinds of cancers and not for others".[This paper has attracted much attention. See, for example, Cancer Stem Cells May Not Be the Supervillains We Thought by Alexis Madrigal, Wired Science, December 3, 2008].

The article in The Globe & Mail ends with a paragraph about the hope that "new drug combinations that target all cell types" [associated with tumors] will be found, and a quote from William Hahn: "Whether the hypothesis is correct or incorrect in its full-blown beauty is really not important in the end" . [What really matters, from a clinical perspective, is whether or not efforts to target CSCs, in addition to other kinds of cells associated with tumors, will lead to improved outcomes for patients].

The article has already attracted some comments from readers.

Disclosure: I'm a co-author of some early papers about the CSC hypothesis, such as: J Natl Cancer Inst 1983(Jan); 70(1): 9-16.

Two reviews about oncolytic viruses

2009-08-27T19:19:00.007-04:00

1) Oncolytic adenoviruses targeted to cancer stem cells by Joshua J Short and David T Curiel, Mol Cancer Ther 2009(Aug); 8(8): 2096-102 [Epub 2009(Aug 11)][PubMed Citation].

2) Targeting cancer-initiating cells with oncolytic viruses by Timothy P Cripe and 4 co-authors, including Patrick WK Lee, Mol Ther 2009(Aug 11) [Epub ahead of print][PubMed Citation].

[Found via CSC-related articles bookmarked in Connotea].

Review of current knowledge on pancreatic CSC

2009-08-27T18:34:00.002-04:00

Role of cancer stem cells in pancreatic ductal adenocarcinoma by Gregory Sergeant, Hugo Vankelecom, Lies Gremeaux and Baki Topal, Nat Rev Clin Oncol 2009(Aug 18) [Epub ahead of print]. PubMed Abstract:

As our understanding of pancreatic cancer evolves, evidence is growing to support a role for cancer stem cells in this devastating disease. Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis; these cells are thought to be highly resistant to standard treatment modalities. Here we review the current knowledge on pancreatic cancer stem cells and the implementation of cancer stem cell markers as prognostic or predictive biomarkers. We also discuss prospects for the use of cancer stem cells as targets for future therapeutic regimens in pancreatic cancer.

[Found via CSC-related articles bookmarked in Connotea].

Cancer Stem Cell News

Cancer Stem Cell Chronicle

A difference between normal and cancer SC biology in the nervous system

Two new initiatives from the CSCC

From the Editor

Trials to target CSCs

OA Video Protocol from Matsui Lab

Insights into the stem cells of CML

Critical molecular pathways in CSCs of CML

Must the last CML cell be killed?

On the low frequency of tumor-initiating cells

Some breast cancer tumors may not originate from stem cells?

Isolation and killing of candidate CML stem cells by antibody targeting

Two Open Access reviews

Selective targeting of neuroblastoma tumour-initiating cells

Therapeutic implications of colon CSCs

Putative tumor-initiating progenitor cells predict poor lung cancer prognosis

Partnership Pays Off

Oxygen, hypoxia and the stem cell niche

Cell of origin for human prostate cancer

Disagreement about melanoma CSCs

Researchers Study CSCs as Therapeutic Targets for Mesothelioma

Prostate CSCs sensitive to gamma-tocotrienol?

Irradiating brain's stem cell niche

More about salinomycin

Innovative Researcher Vlog

Two recent OA articles

CSC news update 2010-07-03

Melanoma-initiating cells identified

CSC news update 2010-06-26

On glioma recurrence and CSCs

OncoMed Has 'Wnt' in its Sails

CIRM and Wisconsin sign a Declaration of Cooperation

Patent application: Levels of Oct1 as a method of identifying CSCs

Decitabine may target ovarian CSCs?

CSC news update 2010-06-13

CSCs responsible for metastasis identified

Phase I clinical trial of ICT-107

Patent application involving miRNAs and CSCs

CSC news update 2010-05-24

An evolving concept of CSCs in tumor biology

US Patent: Isolation and use of solid tumor stem cells

Generic drug a potential treatment for glioblastoma?

CSC news links 2010-05-08

CSC news links 2010-05-01

More about presentations at AACR10

Sessions on CSC Therapeutics at AACR10

CSC news links 2010-04-18

MicroRNA therapy could be a powerful tool to correct the CSC dysregulation?

CSC news roundup 2010-04-11

CFI practices called “world’s best’’

CSC news roundup 2010-03-27

CSC news roundup 2010-03-16

Conditioned medium induces generation of side population cells

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

CSC news roundup 2010-02-28

Targeting A20 Decreases Glioma SC Survival and Tumor Growth

Progression of primary tumours and metastases

CSC news roundup 2010-02-13

Review about retroviral-induced leukemogenesis and the CSC hypothesis

CSC news roundup 2010-01-31

Analyzing tumors as ecosystems

Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic SC

CSC suppress immune response against brain tumor

CSC news roundup 2010-01-16

US Patent 7632678 about CSC

CSC news roundup 2010-01-03

Aging, inflammation and cancer

CSC news roundup 2009-12-24

MK-0752 kills lingering breast CSC

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

Differences that separate normal vs cancer SC molecular circuitry

Twist modulates breast CSC

More about IMUC

CSC news roundup 2009-11-26

IMUC letter to shareholders

Targeting of AML-leukemic SC with monoclonal antibodies

CSC news roundup 2009-11-10

Heterogeneity in the AML stem cell pool

Featured Article in Cell Stem Cell (Nov 09)