Category Archives: Stem Cell Therapy

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.

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.

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].

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 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."

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."

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, and Sankara Nethralaya, http://www.sankaranethralaya.org, announced today commencement of a collaboration to develop ISCO's 'CytoCor™' stem cell-derived corneal tissue. The goal is to use CytoCor to treat corneal blindness and vision impairment. 'This is one more step in ISCO's stated plan of building its portfolio of therapeutic agents through strategic alliances throughout the world,' said Chairman, Ken Aldrich.

CytoCor consists of transparent human tissue derived from pluripotent human stem cells. These structures are produced in the laboratory and recent testing at Sankara Nethralaya and laboratories in the US has demonstrated a range of structural, biochemical and refractory properties characteristic of human cornea.

CytoCor may offer a first-in-class opportunity for high-quality, cost-efficient transplantation tissue for the 10 million people world-wide suffering from corneal vision impairment, particularly in India and the rest of Asia, as well as in Europe. Standardized tissues derived from pluripotent stem cells, such as the CytoCor tissue, could eliminate the current problem that corneal tissue derived from donors may harbor diseases that could be transferred from the donor to the recipient. It may also provide a much needed alternative to the use of live and extracted animal eyes in the $500+million market for safety testing of drugs, chemicals and consumer products.

According to Professor Dr. S. Krishnakumar, 'Sankara Nethralaya is dedicated to the development and application of new state-of-the-art ophthalmic technologies. The need for high-volume, high-quality human corneal tissue is substantial, not only in India but across Asia and much of Europe. We appreciate the opportunity to join ISCO in their pursuit to create a new standard of care for the treatment of human corneal disease.' Initially, Dr. Krishnakumar and his team will be using the CytoCor tissue in preclinical studies to explore the ability of the tissue to withstand sutures and bio-compatible glues in order to validate the potential of the tissue for use in animal or human clinical trials.

According to Dr. Geetha Krishnan Iyer, who is involved in the management of ocular surface disease at Sankara Nethralaya, 'The team at Sankara Nethralaya is pleased to collaborate with ISCO on stem cell-derived corneal tissue. In vitro studies to evaluate safety and efficacy of the tissue, as well as surgical feasibility tests will be carried out, following which there could be clinical application in lamellar keratoplasty using the above mentioned tissue. With improvements in surgical techniques over the past few years, the indications for anterior lamellar keratoplasty have expanded significantly. With high demand for donor corneal tissue for the same but limited availability, there is definitely scope for utilizing ISCO's corneal tissue following relevant tests.'

Jeffrey Janus, Senior VP of Operations at ISCO, states: 'This collaboration with the excellent team of scientists and clinicians at Sankara Nethralaya has already proven to be productive. Sankara's ophthalmology expertise and ISCO's cell culture capabilities constitute a perfect match to perfect and advance CytoCor tissue towards future use in treating corneal disease and injuries.'

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). These proprietary cells avoid ethical issues associated with use or destruction of viable human embryos and, unlike all other major stem cell types, can be immune matched and be a source of therapeutic cells with minimal rejection after transplantation into hundreds of millions of individuals across racial groups. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and is developing a line of cosmeceutical products via its subsidiary Lifeline Skin Care. ISCO is advancing novel human stem cell-based therapies where cells have been proven to be efficacious but traditional small molecule and protein therapeutics have not. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and therapeutic applications, the potential benefits of collaborations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, and Sankara Nethralaya, http://www.sankaranethralaya.org, announced today commencement of a collaboration to develop ISCO's 'CytoCor™' stem cell-derived corneal tissue. The goal is to use CytoCor to treat corneal blindness and vision impairment. 'This is one more step in ISCO's stated plan of building its portfolio of therapeutic agents through strategic alliances throughout the world,' said Chairman, Ken Aldrich.

CytoCor consists of transparent human tissue derived from pluripotent human stem cells. These structures are produced in the laboratory and recent testing at Sankara Nethralaya and laboratories in the US has demonstrated a range of structural, biochemical and refractory properties characteristic of human cornea.

CytoCor may offer a first-in-class opportunity for high-quality, cost-efficient transplantation tissue for the 10 million people world-wide suffering from corneal vision impairment, particularly in India and the rest of Asia, as well as in Europe. Standardized tissues derived from pluripotent stem cells, such as the CytoCor tissue, could eliminate the current problem that corneal tissue derived from donors may harbor diseases that could be transferred from the donor to the recipient. It may also provide a much needed alternative to the use of live and extracted animal eyes in the $500+million market for safety testing of drugs, chemicals and consumer products.

According to Professor Dr. S. Krishnakumar, 'Sankara Nethralaya is dedicated to the development and application of new state-of-the-art ophthalmic technologies. The need for high-volume, high-quality human corneal tissue is substantial, not only in India but across Asia and much of Europe. We appreciate the opportunity to join ISCO in their pursuit to create a new standard of care for the treatment of human corneal disease.' Initially, Dr. Krishnakumar and his team will be using the CytoCor tissue in preclinical studies to explore the ability of the tissue to withstand sutures and bio-compatible glues in order to validate the potential of the tissue for use in animal or human clinical trials.

According to Dr. Geetha Krishnan Iyer, who is involved in the management of ocular surface disease at Sankara Nethralaya, 'The team at Sankara Nethralaya is pleased to collaborate with ISCO on stem cell-derived corneal tissue. In vitro studies to evaluate safety and efficacy of the tissue, as well as surgical feasibility tests will be carried out, following which there could be clinical application in lamellar keratoplasty using the above mentioned tissue. With improvements in surgical techniques over the past few years, the indications for anterior lamellar keratoplasty have expanded significantly. With high demand for donor corneal tissue for the same but limited availability, there is definitely scope for utilizing ISCO's corneal tissue following relevant tests.'

Jeffrey Janus, Senior VP of Operations at ISCO, states: 'This collaboration with the excellent team of scientists and clinicians at Sankara Nethralaya has already proven to be productive. Sankara's ophthalmology expertise and ISCO's cell culture capabilities constitute a perfect match to perfect and advance CytoCor tissue towards future use in treating corneal disease and injuries.'

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). These proprietary cells avoid ethical issues associated with use or destruction of viable human embryos and, unlike all other major stem cell types, can be immune matched and be a source of therapeutic cells with minimal rejection after transplantation into hundreds of millions of individuals across racial groups. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and is developing a line of cosmeceutical products via its subsidiary Lifeline Skin Care. ISCO is advancing novel human stem cell-based therapies where cells have been proven to be efficacious but traditional small molecule and protein therapeutics have not. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and therapeutic applications, the potential benefits of collaborations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligatio
n to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

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."

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."