Friday, October 31, 2008

CD133+ cells within osteosarcoma cell lines

Detection and characterization of CD133+ cancer stem cells in human solid tumours by Virginia Tirino and 8 co-authors, including Gianpaolo Papaccio, PLoS ONE 2008(Oct 21); 3(10): e3469. PubMed Abstract:
BACKGROUND: Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency. CONCLUSIONS: Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer.
The full text of this article is openly accessible.

Tuesday, October 28, 2008

Single-cell cloning of colon cancer stem cells

Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity by Louis Vermeulen and 8 co-authors, including Jan Paul Medema, Proc Natl Acad Sci USA 2008( Sep 9);105(36): 13427-32. PubMed Abstract:
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear beta-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.

Saturday, October 25, 2008

Two articles about brain tumor initiating cells

Hedgehog signaling regulates brain tumor initiating cell proliferation and portends shorter survival for patients with PTEN-coexpressing glioblastomas by Qijin Xu, Xiangpeng Yuan, Gentao Liu, Keith L Black, John S Yu, Stem Cells 2008(Sep 11) [Epub ahead of print][PubMed Citation].

SOX2 silencing in glioblastoma tumor initiating cells causes stop of proliferation and loss of tumorigenicity by Rosaria Maria Rita Gangemi and 9 co-authors, including Giorgio Corte, Stem Cells 2008(Oct 23) [Epub ahead of print][PubMed Citation].

Neither of these articles is openly accessible.

UK/CIRM collaboration agreement

State, United Kingdom team for stem cell work by Bernadette Tansey, SFGate, October 21, 2008. Excerpts:
California's stem cell funding institute is teaming up with its United Kingdom counterpart to support research collaborations between scientists, the two government agencies said Monday.
.....
Under the new agreement, teams that include United Kingdom and California scientists will be able to file joint grant applications to the state's stem cell funding institute and the United Kingdom's Medical Research Council. For teams that win grants, the California institute will fund the work of the California members and the research council will pay for the research conducted in the United Kingdom.
.....
The state stem cell funding institute announced similar agreements in June with the Australian state of Victoria and Canada's Cancer Stem Cell Consortium. Victoria pledged $100 million to the effort.
Found via: UK, CIRM ink collaboration agreement by David Jensen, California Stem Cell Report, October 22, 2008.

See also: UK and California agree to collaborate on stem cell research by Monya Baker, The Niche, October 21, 2008. The first two paragraphs:
California’s stem cell funding agency signed a memorandum of understanding with the United Kingdom, expediting collaborations between scientists in the two locations.

Robert Klein, chair of the California Institute of Stem Cell Research and Lord Paul Drayson, UK’s Minister for Science, met in the San Francisco airport to sign the four-page document.

Thursday, October 23, 2008

CIRM/CSCC Joint Announcement: Disease Teams Awards

The Cancer Stem Cell Consortium and the California Institute for Regenerative Medicine Announce Plans to Collaborate on Disease Team Awards, News & Media, Cancer Stem Cell Consortium.
At the BIO 2008 Conference in June, the Canadian Minister of Health, the Honourable Tony Clement, and the Governor of the State of California, Arnold Schwarzenegger announced a partnership between Canada's Cancer Stem Cell Consortium (CSCC) and the California Institute for Regenerative Medicine (CIRM) for international collaboration to advance cancer stem cell research.

It is proposed that one of the first initiatives to be launched by the CSCC will be a collaboration between Canadian and Californian scientists through CIRM's upcoming Disease Team Research Awards Competition, which will support multi-disciplinary teams of scientists in pursuit of therapies for specific diseases. The goal is to fund the work of Disease Teams that would result in a cell based therapy or a therapy derived from stem cell assays for a particular disease or serious injury. It is anticipated that the RFA for the Disease Team Research Awards will be issued by CIRM in February 2009 with funding announced before the end of the year. Successful proposals will include a description of milestones on a path to an Investigational New Drug filing at the end of the four-to-five year grant.

CIRM and the CSCC have been working to finalize the details of the collaboration, with approval to be requested later this year from their respective governing bodies. In advance of the formal approval and announcement, the organizations wish to alert the Canadian and Californian scientific communities of this potential opportunity and to encourage teams of Canadian and Californian scientists to initiate activities towards the development of Disease Teams focusing on cancer stem cells. Successful projects, co-led by Canadian and California scientists, will be co-funded by the CSCC and CIRM, with Canadian scientists funded by the CSCC and Californian scientists funded by CIRM. Support for Canadian scientists will primarily be for operating funds and will not include support for major infrastructure or facilities.

Canadian scientists proposing to collaborate with Californian colleagues in a joint Disease Team application must register with the CSCC as soon as possible and no later than November 17, 2008. Applications for funding will be reviewed by CIRM's Grants Working Group as part of the Disease Team Research Awards Competition.
To register to submit an application please contact:
Cindy L. Bell, Ph.D.
Interim Executive Director
Cancer Stem Cell Consortium
http://www.cancerstemcellconsortium.ca
Phone: 613-751-4460 ext 118
cbell@genomecanada.ca

Making an anti-leukemia drug better

Making an Anti-leukemia Drug Better, Ivanhoe's Medical Breakthroughs, October 21, 2008. The first sentence:
A recent discovery suggests the best way to treat leukemia may be to rely on a combination of targeted drugs rather than a single miracle drug.
The drug is imatinib.

The news item is based on: AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells by Liang L Zhou and 9 co-authors, including Xiaoyan Jiang, J Exp Med 2008(Oct 20): jem.20072316. [Epub ahead of print]. PubMed Abstract:
Chronic myeloid leukemia (CML) represents the first human malignancy successfully treated with a tyrosine kinase inhibitor (TKI; imatinib). However, early relapses and the emergence of imatinib-resistant disease are problematic. Evidence suggests that imatinib and other inhibitors may not effectively eradicate leukemic stem/progenitor cells, and that combination therapy directed to complimentary targets may improve treatment. Abelson helper integration site 1 (Ahi-1)/AHI-1 is a novel oncogene that is highly deregulated in CML stem/progenitor cells where levels of BCR-ABL transcripts are also elevated. Here, we demonstrate that overexpression of Ahi-1/AHI-1 in murine and human hematopoietic cells confer growth advantages in vitro and induce leukemia in vivo, enhancing effects of BCR-ABL. Conversely, RNAi-mediated suppression of AHI-1 in BCR-ABL-transduced lin(-)CD34(+) human cord blood cells and primary CML stem/progenitor cells reduces their growth autonomy in vitro. Interestingly, coexpression of Ahi-1 in BCR-ABL-inducible cells reverses growth deficiencies exhibited by BCR-ABL down-regulation and is associated with sustained phosphorylation of BCR-ABL and enhanced activation of JAK2-STAT5. Moreover, we identified an AHI-1-BCR-ABL-JAK2 interaction complex and found that modulation of AHI-1 expression regulates phosphorylation of BCR-ABL and JAK2-STAT5 in CML cells. Importantly, this complex mediates TKI response/resistance of CML stem/progenitor cells. These studies implicate AHI-1 as a potential therapeutic target downstream of BCR-ABL in CML.
See also: Giving imatinib a hand, Amy Maxmen, J Exp Med 2008(Oct 20): jem.20511iti5

Sunday, October 19, 2008

Nestin expression in osteosarcomas

Nestin expression in osteosarcomas and derivation of nestin/CD133 positive osteosarcoma cell lines by Renata Veselska, Marketa Hermanova, Tomas Loja, Petr Chlapek, Iva Zambo, Karel Vesely, Karel Zitterbart and Jaroslav Sterba, BMC Cancer 2008(Oct 16); 8(1): 300. PubMed Abstract:
BACKGROUND: Nestin was originally identified as a class VI intermediate filament protein that is expressed in stem cells and progenitor cells in the mammalian CNS during development. This protein is replaced in the adult organism by other intermediate filament proteins; however, nestin may be re-expressed under certain pathological conditions such as ischemia, inflammation, brain injury, and neoplastic transformation. Nestin has been detected in many kinds of tumors, especially in tumors derived from the CNS. Co-expression of nestin and the CD133 surface molecule is considered to be a marker for cancer stem cells in neurogenic tumors. Our work was aimed at a detailed study of nestin expression in osteosarcomas and osteosarcoma-derived cell lines. METHODS: Using immunodetection methods, we examined nestin in tumor tissue samples from 18 patients with osteosarcomas. We also successfully established permanent cell lines from the tumor tissue of 4 patients and immunodetection of nestin and CD133 was performed on these cell lines. RESULTS: Nestin-positive tumor cells were immunohistochemically detected in all of the examined osteosarcomas, but the proportion of these cells that were positively stained as well as the intensity of staining varied. Nestin-positive cells were rarely observed in 2 tumor samples, and the remaining 16 tumor samples showed various nestin expression patterns ranging from very sporadic occurrence to an overwhelming proportion of cells with strong positive staining. Three of the established osteosarcoma cell lines were demonstrated to be nestin-positive, and only one cell line showed no expression of nestin; this finding corresponds with the rare occurrence of nestin-positive cells in the respective tumor sample. Moreover, three of these osteosarcoma cell lines were undoubtedly proven to be Nes+/CD133+. CONCLUSIONS: Our results represent the first evidence of nestin expression in osteosarcomas and suggest the possible occurrence of cells with a stem-like phenotype in these tumors.
The full text is openly accessible.

Found via Nestin expression in osteosarcomas and derivation of nestin/CD133 positive osteosarcoma cell lines, 7thSpace Interactive, October 16, 2008.

Breast cancer stem cells hard to kill?

Breast cancer stem cells may be hardest to kill by John Miner, The London Free Press, October 11, 2008. (Archived by WebCite® at http://www.webcitation.org/5bgoyZhVX). The first two paragraphs:
A London researcher is investigating the possibility that the most dangerous breast cancer cells also are the hardest to kill with chemotherapy and radiation.
Alysha Croker, a trainee at the Lawson Health Research Institute, and graduate student at the University of Western Ontario, has already established cancer cells within a tumour can play different roles.
The article appears to be based on a press release: "Bright, Young Minds at Lawson Fight Breast Cancer" [PDF] from the Lawson Health Research Institute (London, Ontario, Canada) dated September 10, 2008. The first paragraph:
The future of breast cancer treatment may involve targeting cancerous stem-like cells (cancer stem cells). These cancer stem cells have recently been identified as the cells that initiate and maintain tumor growth. The same cells seem to play a key role in breast cancer metastasis. What is more, these cells may be resistant to both radiation and chemotherapy. Alysha Croker, a trainee at Lawson Health Research Institute (Lawson) and a graduate student at the Schulich School of Medicine & Dentistry at The University of Western Ontario (Western), has been awarded a fellowship from the Canadian Breast Cancer Foundation (CBCF) to investigate the behaviour and response of cancer stem cells to commonly used chemotherapy agents and to radiation.
The Canadian Breast Cancer Foundation (CBCF) "allocates funds to high-quality research and community grants" across Canada.

Alysha Croker has worked under the guidance of Alison L Allan, an Oncology Scientist at the London Regional Cancer Program. For a recent review based on their work, see: Cancer stem cells: implications for the progression and treatment of metastatic disease by Alysha K Croker and Alison L Allan, J Cell Mol Med 2008(Apr); 12(2): 374-90. On October 19, 2008, both the HTML and PDF versions of the full-text were freely accessible. The PubMed Abstract:
Metastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re-initiate tumour growth to form life-threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess "stem-like" characteristics. Classical properties of normal stem cells are strikingly reminiscent of the observed experimental and clinical behaviour of metastatic cancer cells, including an unlimited capacity for self renewal; the requirement for a specific 'niche' or microenvironment to grow; use of the stromal cell-derived factor 1 (SDF-1)/chemokine receptor 4 (CXCR4) axis for migration; enhanced resistance to apoptosis and an increased capacity for drug resistance. Therefore, in addition to playing a role in primary tumour formation, we believe that CSCs are also key players in the metastatic process. We will review the current evidence supporting this idea and discuss the potential implications of the CSC hypothesis with regards to experimental investigation and treatment of metastatic disease.
The Journal of Cellular and Molecular Medicine is published by Wiley-Blackwell, which offers a hybrid Open Access option called OnlineOpen. For 2008, the OnlineOpen fee is US$3000. See also the Journal of Cellular and Molecular Medicine Open Access Exclusive Licence Form [PDF].

Delayed OA, after an embargo period, is also available free of charge. According to the Journal of Cellular and Molecular Medicine Exclusive Licence Form [PDF], "12 months after publication you may post an electronic version of the Article on your own personal website, on your employer’s website/repository and on free public servers in your subject area" but "you are not permitted to post the Blackwell Publishing PDF version of the Article online". Some Wiley-Blackwell journals make their backfiles openly accessible after an embargo period (usually, a year or more), but the Journal of Cellular and Molecular Medicine isn't included in the current list of such journals. (See the section entitled "Wiley-Blackwell Open Access Backfiles" in the page entitled "Wiley-Blackwell and Open Access").

Added October 20, 2008:

See also another recent article: High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability by Alysha K Croker and 6 co-authors, including Alison L Allan, J Cell Mol Med 2008(Aug 4). [Epub ahead of print]. [PubMed Abstract]. A PDF version of the full text of this article is currently freely accessible.

Saturday, October 18, 2008

Koch’s postulates and cancer stem cells

Cancer stem cells: Beyond Koch’s postulates by Emmanuel Garcion, Philippe Naveilhan, Fran├žois Berger, Didier Wion. Cancer Letters, in press. Corrected proof available online 14 October 2008.

Abstract:
Until the last century, infectious diseases were the leading cause of human mortality. Therefore, our current medical reasoning is profoundly influenced by views that originated from medical microbiology. The notion that cancer growth is sustained by a sub-population of particular cells, the cancer stem cells, is highly reminiscent of the germ theory of disease as exemplified by Koch’s postulates in the XIXth century. However, accumulating data underscore the importance of cell-cell interactions and tumor environment. Hence it is essential to critically review the basic tenets of the cancer stem cell concept on the light of their relationships with Koch’s postulates. Shifting the pathogenic element from a special cellular entity (cancer stem cell or microorganism) to a “pathogenic field” could be critical for curing both cancer and drug-resistant infectious diseases.
Excerpt from the "Concluding remarks" in the full text (which isn't freely-accessible):
Indeed, the reductionist and oversimplified cancer stem cell paradigm which originates from the implicit application of Koch’s postulates should progressively evolve towards a “tumorigenic field” concept, just as the “one gene _ one protein _ one phenotype” paradigm has evolved towards epistasis ...

Wednesday, October 15, 2008

Patent application: cancer stem cell vaccine technology

ImmunoCellular Therapeutics Announces Filing Of Patent Application For A Novel Cancer Stem Cell Vaccine Technology, Medical News Today, October 12, 2008. The first paragraph:
ImmunoCellular Therapeutics, Ltd. (OTC: IMUC) (IMUC), a biotechnology company, announced the filing of a provisional U.S. patent application relating to its novel vaccine technology targeting cancer stem cells. The vaccine technology is exclusively licensed from Cedars-Sinai Medical Center. The patent claims are broad and include compositions of peptides for cancer immunotherapy as well as methods for inducing immune responses against tumor antigens in cancer patients.

Monday, October 13, 2008

The Year in Hormones and Cancer Lecture

COMMENTARY: The Year in Hormones and Cancer Lecture: Update of Estrogen plus Progestin Therapy for Menopausal Hormone Replacement Implicating Stem Cells in the Increased Breast Cancer Risk by Kathryn B. Horwitz, Mol Endocrinol 2008(Oct 9) [Epub ahead of print]. [PubMed Abstract]:
This transcript is based on my "The Year in Hormones & Cancer" lecture at ENDO 08 that reviewed current data surrounding hormone replacement therapy (HRT); the relationship between systemic estrogen plus progestin (E+P) treatment and increased breast cancer risk; and explored the hypothesis that women who "develop" breast cancer while on E+P had occult, undiagnosed disease before they started therapy. Beginning with recent HRT data focusing on E+P and its association with breast cancer to set the stage, the lecture then reviewed our newly published data that progestins expand breast cancer stem cells. Finally, the issues of occult or undiagnosed breast cancer in presumably healthy women, and of tumor dormancy in breast cancer survivors, were brought to bear on the discussion. Taken together, these apparently disparate themes allowed me to suggest the idea that systemic progestins have the ability to reawaken cancers that were presumed to be either nonexistent or cured. To avoid this potentially devastating outcome while retaining the benefits of E+P, I advocated the use of local progestin delivery methods, rather than the currently popular systemic routes.
The last two sentences of the "Conclusions" section in the (freely-accessible) PDF version of the full text:
There is considerable evidence for the presence of undetected, possibly undetectable, microdisease in a relatively substantial population of women - both in women who have no evidence of disease, as well as in women who have had breast cancer and are believed to be disease-free. I believe that systemic HRT, especially the progestin component, could be dangerous to such women.

Sunday, October 12, 2008

Stanford center for stem cell research

Lokey gives $75 million to create nation's largest stem cell research center at Stanford by Ruthann Richter (News Release, Office of Communication & Public Affairs, Stanford University Medical Center, October 6, 2008). Excerpts:
Lorry I. Lokey, the Business Wire founder and philanthropist, is giving $75 million to the Stanford University School of Medicine to help build what is expected to be the nation’s largest center for stem cell research, the medical school announced Oct. 6.
.....
His contribution will help build a new home for the Stem Cell Biology and Regenerative Medicine Institute, one of five major research institutes based in the medical school. Institute scientists are involved in the full array of stem cell research, including studies in both embryonic and adult cells, as well as work in cancer stem cells and in the development of disease-specific stem cell lines.
.....
“Scientists in the fields of stem cell and cancer research are on the brink of new discoveries that may soon affect the understanding and treatment of disease,” said Irving Weissman, MD, the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research and director of Stanford’s stem cell institute. “With this magnificent lead gift from Lorry Lokey, Stanford will have the facilities to lead those efforts.”

Weissman, who was the first to isolate stem cells in both mice and humans, said the availability of new space will attract key faculty to Stanford and spur collaborations with scientists from the around the world. The new center will include 60 laboratory benches for scientists who will visit Stanford for a month or a year at a time. Lokey said the prospect of bringing top research talent to Stanford is far more meaningful to him than any worldly goods his money could buy.

“I don’t want airplanes and boats and country club memberships,” he said. “I believe that if you fall into a lot of money like I did, you put it into the soil—you replenish the soil for next year’s crop.”
Found via MarketWatch, Oct 06, 2008.

Thursday, October 9, 2008

Translational research for medical interventions

Tracking the lag between promise and payoff by Janet D. Stemwedel, Adventures in Ethics and Science, October 2, 2008. This blog post isn't about cancer stem cells, but is of interest because it's focus is on translational research for medical interventions. Excerpts:
One of the reasons non-scientists see science as at all valuable is that scientific research may result in useful medical treatments. And one of the aspects of science that seems elusive to non-scientists is just how long it can take scientific research to bring those useful medical treatments about.
.....
The time interval between the first report on preparation, isolation, or synthesis (or the earliest patent) and the highly cited articles reporting successful clinical interventions -- between the report of findings with clinical potential and the determination via clinical trials that that promise is realized in a treatment -- is the "translational lag". (There is, of course, another lag that's harder to quantify this way -- that between the initial findings in the research lab and the publication of those findings.)
Contopoulos-Ioannidis et al. found that the median translational lag for the highly cited article[s] in their study was 24 years. That's a long time.
The blog post is based on this article: Life Cycle of Translational Research for Medical Interventions, by Despina G. Contopoulos-Ioannidis, George A. Alexiou, Theodore C. Gouvias, John P. A. Ioannidis, Science 2008(Sep 5); 321(5894): 1298-9 [PubMed Citation]. The article isn't freely accessible, and has no abstract. The brief Summary:
From the initial discovery of a medical intervention to a highly cited article is a long road, and even this is not the end of the journey.
An excerpt from the final section of the full text:
The following are some recommendations for improving the system, based on our analyses:
• Discovery of new substances and interventions remains essential, but proper credit and incentives should be given to accelerate the testing of these applications in high-quality, unbiased clinical research and the replication of claims for effectiveness.
• Multidisciplinary collaboration with focused targets and involving both basic and clinical sciences should be encouraged.
• Proof of effectiveness for new interventions requires large, robust randomized clinical trials.
• Translational efforts for common diseases should focus more on novel agents and new cutting-edge technologies; for these ailments, it is unlikely that genuine major benefits from interventions already known for a long time have gone unnoticed.
Comments: Of the 32 interventions highlighted in this study, only two were cancer-related:

1) Levamisole (with Fluorouracil): Colon cancer
• Date of highly cited study: 1990
• Date of first description of intervention: 1966
• Report of first human use: 1977
2) Tamoxifen: Breast cancer prevention
• Date of highly cited study: 1998
• Date of first description of intervention: 1964
• Report of first human use: 1971
For cancer stem cells, what might be an important first intervention to be described? Proof that the eradication of cancer stem cells from a patient's tumor is therapeutic?

Perhaps a clinical demonstration that cancer stem cells can be used as a prognostic indicator of disease progression wouldn't be regarded as a "therapeutic intervention", but it's a key challenge for those doing research on cancer stem cells. See, for example, a review by Eric Lagasse, Gene Ther 2008(Jan); 15(2): 136-42 [PubMed Abstract]. Excerpt from the full text (not freely accessible):
[Remaining challenges] include the clinical demonstration that cancer stem cells can be used as a prognostic indicator of disease progression and proof that the eradication of cancer stem cells from a patient's tumor is therapeutic.

Sunday, October 5, 2008

Cell fate in human multipotent colorectal cancer cells

Alpha2 Beta1 integrin regulates lineage commitment in multipotent human colorectal cancer cells by Susan C. Kirkland and Huijun Ying, J Biol Chem 2008(Oct 10); 283(41): 27612-19. The last sentence of the Abstract:
This study indicates that the collagen receptor alpha2beta1 integrin is a regulator of cell fate in human multipotent colorectal cancer cells.
This is an Author Choice (hybrid OA) article, licensed with a Creative Commons Attribution Non-Commercial License.

Thursday, October 2, 2008

Review article in Urologic Oncology

"Cancer stem cells"-Lessons from Hercules to fight the Hydra, by Felix Roman Moltzahn, Jens-Peter Volkmer, Daniel Rottke, Rolf Ackermann. Urol Oncol 2008 Sep 23. [Epub ahead of print]. Abstract:
Following the initial identification of hematopoietic tumor stem cells, such cells were also found in several solid tumor types. In urology, cancer stem cells have only been found in prostate tumors so far. The concept and detection of tumor stem cells rely heavily on findings derived from stem cell research. Therefore, in addition to identifying and characterizing urologic tumor stem cells, research in uro-oncology should also aim at better understanding the stem-cell biology of urologic organs. Insights in similarities and differences gleaned from these studies could be used to develop strategies for targeted destruction of tumor stem cells while sparing the physiological stem cells. The main target of future curative therapies in uro-oncology must therefore be the central, immortal head of the Hydra, the tumor stem cell.
Excerpt from the full text:
3. CSC definition
The tumor stem cell is the original cell of the tumor, responsible for tumorigenesis, tumor differentiation, tumor maintenance, and also for tumor spread and tumor relapse. This is analogous to a stem cell being the original cell of an organ, responsible for organogenesis and organ maintenance.
Unfortunately, the full text isn't freely-accessible. The publisher (Elsevier) permits the peer-reviewed postprint to be archived on authors' personal or authors' institution's server (see the SHERPA/RoMEO entry for Urologic Oncology). However, a Google search didn't reveal a freely-accessible version of this review.