StemCell Therapy

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.

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.

The following is an excerpt from the August 3, 2010 Breakthrough Technology Alert, published by Agora Financial. Agora Financial is a fully independent publisher and has no financial connections to companies listed below. Breakthrough Technology Alert's editor is industry expert Patrick Cox. Patrick is renowned for his innovative forecasts and keeping readers "ahead of the story".

For more information about Patrick Cox and Breakthrough Technology Alert please visit http://www.agorafinancial.com

ISCO Collaborations Accelerate

Last week, I told you about International Stem Cell Corp.'s (OTCBB: ISCO) new European subsidiary, ISCO Europe. That announcement closely followed an announced alliance with a leading Indian provider of corneal transplants. Now ISCO has announced that it has entered into a distribution agreement for its Lifeline brand of human cell culture products in India.

Jeffrey Janus, senior vice president of operations of ISCO and CEO of its subsidiary Lifeline, said in a press release, Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.

For transformational profits,

Patrick Cox

To learn more about Patrick Cox and Breakthrough Technology Alert please click here. © 2010 by Agora Financial, LLC. 808 St. Paul Street, Baltimore, MD 21202. All rights reserved. No part of this report may be reproduced by any means or for any reason without the consent of the publisher. The information contained herein is obtained from sources believed to be reliable; however, its accuracy cannot be guaranteed.

The following is an excerpt from the August 3, 2010 Breakthrough Technology Alert, published by Agora Financial. Agora Financial is a fully independent publisher and has no financial connections to companies listed below. Breakthrough Technology Alert's editor is industry expert Patrick Cox. Patrick is renowned for his innovative forecasts and keeping readers "ahead of the story".

For more information about Patrick Cox and Breakthrough Technology Alert please visit http://www.agorafinancial.com

ISCO Collaborations Accelerate

Last week, I told you about International Stem Cell Corp.'s (OTCBB: ISCO) new European subsidiary, ISCO Europe. That announcement closely followed an announced alliance with a leading Indian provider of corneal transplants. Now ISCO has announced that it has entered into a distribution agreement for its Lifeline brand of human cell culture products in India.

Jeffrey Janus, senior vice president of operations of ISCO and CEO of its subsidiary Lifeline, said in a press release, Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.

For transformational profits,

Patrick Cox

To learn more about Patrick Cox and Breakthrough Technology Alert please click here. © 2010 by Agora Financial, LLC. 808 St. Paul Street, Baltimore, MD 21202. All rights reserved. No part of this report may be reproduced by any means or for any reason without the consent of the publisher. The information contained herein is obtained from sources believed to be reliable; however, its accuracy cannot be guaranteed.

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].

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].

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.

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, via its wholly-owned subsidiary, Lifeline Cell Technology® (Lifeline) http://www.lifelinecelltech.com, and Sristi Biosciences, http://www.sristibio.com, have entered into a distribution agreement for the Lifeline® brand of human cell culture products in India.

Lifeline specializes in development, manufacture and distribution of primary human cells and media and growth factors for optimized culturing of cells, including stem cells. These products are being requested by customers internationally, including in India, which represents one of the fastest growing markets for products of this kind.

According to Lifeline's CEO and SVP of Operations at ISCO, Jeffrey Janus, 'Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.'

Lifeline's scientists have over 20 years of experience developing products for the culture of human cells. The company has made significant contributions to the creation and standardization of human cell systems used today for clinical applications and in academic, government and pharmaceutical research laboratories. The group sells over 75 standardized products directly and via its distributors in the US and abroad. It also engages in customized product development for its largest customers.

Dr. Sudhir Reddy, Sristi Biosciences' CEO adds, 'We are pleased to be the first company to introduce the Lifeline products to the growing Indian research market. Our cell culture experience and broad market reach in India will benefit the brand and help Sristi Biosciences further accelerate its commercialization and corporate growth in the biomedical field.'

ISCO recently announced the beginning of a collaboration on its human corneal tissue, CytoCor™, with leading Indian eye hospital and research center, Sankara Nethralaya, and Letter of Intent with Insight Bioventures India (IBVI) to seek funding and establishment of development and manufacturing operations for ISCO's research and pharmaceutical products in India (ISCO India), including the Lifeline products and CytoCor.

'The Lifeline distribution agreement with Sristi Biosciences is central to ISCO's international expansion. Besides facilitating commercialization of the Lifeline products in India, Sristi Biosciences' cell therapy development, regulatory and manufacturing expertise will be important as ISCO and IBVI seek to establish ISCO India with cost-efficient development and manufacturing of research and pharmaceutical products for the Indian and broader Asian markets,' says Brian Lundstrom, ISCO's President.

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 most 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 of differing 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 on ISCO's website.

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.

ABOUT SRISTI BIOSCIENCES

Sristi Biosciences Private Limited is a result of twelve years of research and corporate development in the therapeutic space and is the healthcare component of leading biotechnology group, SRI Biotech, in India. Sristi Biosciences' two main divisions include Tissue Engineering and Cell Therapy that has pioneered chondrocytes-based cell therapy in India and Drug Discoverythat covers the Indian research product market with natural compound libraries, molecular diagnostics and markers, informatics and cell-based products. Sristi's integrated research and development facility in Hyderabad is state-of-the-art and the company has wide collaborative and commercial presence across the research market in India, including 23 leading biotech institutes and major corporate bodies.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated developments and therapeutic applications, the potential benefits of collaborations, affiliations, 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 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

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.

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, via its wholly-owned subsidiary, Lifeline Cell Technology® (Lifeline) http://www.lifelinecelltech.com, and Sristi Biosciences, http://www.sristibio.com, have entered into a distribution agreement for the Lifeline® brand of human cell culture products in India.

Lifeline specializes in development, manufacture and distribution of primary human cells and media and growth factors for optimized culturing of cells, including stem cells. These products are being requested by customers internationally, including in India, which represents one of the fastest growing markets for products of this kind.

According to Lifeline's CEO and SVP of Operations at ISCO, Jeffrey Janus, 'Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.'

Lifeline's scientists have over 20 years of experience developing products for the culture of human cells. The company has made significant contributions to the creation and standardization of human cell systems used today for clinical applications and in academic, government and pharmaceutical research laboratories. The group sells over 75 standardized products directly and via its distributors in the US and abroad. It also engages in customized product development for its largest customers.

Dr. Sudhir Reddy, Sristi Biosciences' CEO adds, 'We are pleased to be the first company to introduce the Lifeline products to the growing Indian research market. Our cell culture experience and broad market reach in India will benefit the brand and help Sristi Biosciences further accelerate its commercialization and corporate growth in the biomedical field.'

ISCO recently announced the beginning of a collaboration on its human corneal tissue, CytoCor™, with leading Indian eye hospital and research center, Sankara Nethralaya, and Letter of Intent with Insight Bioventures India (IBVI) to seek funding and establishment of development and manufacturing operations for ISCO's research and pharmaceutical products in India (ISCO India), including the Lifeline products and CytoCor.

'The Lifeline distribution agreement with Sristi Biosciences is central to ISCO's international expansion. Besides facilitating commercialization of the Lifeline products in India, Sristi Biosciences' cell therapy development, regulatory and manufacturing expertise will be important as ISCO and IBVI seek to establish ISCO India with cost-efficient development and manufacturing of research and pharmaceutical products for the Indian and broader Asian markets,' says Brian Lundstrom, ISCO's President.

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 most 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 of differing 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 on ISCO's website.

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.

ABOUT SRISTI BIOSCIENCES

Sristi Biosciences Private Limited is a result of twelve years of research and corporate development in the therapeutic space and is the healthcare component of leading biotechnology group, SRI Biotech, in India. Sristi Biosciences' two main divisions include Tissue Engineering and Cell Therapy that has pioneered chondrocytes-based cell therapy in India and Drug Discoverythat covers the Indian research product market with natural compound libraries, molecular diagnostics and markers, informatics and cell-based products. Sristi's integrated research and development facility in Hyderabad is state-of-the-art and the company has wide collaborative and commercial presence across the research market in India, including 23 leading biotech institutes and major corporate bodies.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated developments and therapeutic applications, the potential benefits of collaborations, affiliations, 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 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

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].

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].

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).

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 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.

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.

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, announced today that it had entered into a Memorandum of Understanding with ARG Vermogensverwaltung AG ('ARG'), a German Investment Fund, to create a new European subsidiary ('ISCO Europe') to be funded with up to $10 million of capital derived from ARG and other independent sources in Europe. Shares of ISCO Europe are expected to trade on the Deutsche Bourse independently of the company's shares in the US. ISCO Europe's shares will not be convertible into ISCO shares on any US exchange.

ISCO Europe will be licensed by ISCO to develop and market therapeutic products derived from ISCO's technology throughout the Euro Currency Countries and Switzerland. New technologies developed by either ISCO or ISCO Europe will be made mutually available, thus expanding the total funding available to ISCO worldwide without issuing new ISCO shares and enhancing the potential market and scientific development capacity of both companies.

It is expected that the new subsidiary will be funded initially by a private equity investment by ARG and that ARG will then assist in forming an investment group to invest up to $10 million concurrently with the listing of ISCO Europe on the Deutsche Bourse, the largest Securities Exchange in Europe. Following the financing of ISCO Europe, ISCO is expected to retain ownership of 80% or more of this new subsidiary.

'Although negotiations are still at the non-binding memorandum of understanding stage, this transaction, when completed, will expand ISCO's access to capital for worldwide expansion and ISCO's access to new scientific development without requiring equity dilution of ISCO's current shareholders. We are creating an investment, research and development, marketing and distribution entity by adding capital and human resources from Europe to help fulfill ISCO's goal of supplying its proprietary cells and cell therapies to the world,' said Kenneth Aldrich, Chairman and co-founder of ISCO.

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 most 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 of differing 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 on ISCO's website. 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 developments and therapeutic applications, the potential benefits of collaborations, affiliations, 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 forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Andrey Semechkin, Ph.D., CEO
aes@intlstemcell.com

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, announced today that it had entered into a Memorandum of Understanding with ARG Vermogensverwaltung AG ('ARG'), a German Investment Fund, to create a new European subsidiary ('ISCO Europe') to be funded with up to $10 million of capital derived from ARG and other independent sources in Europe. Shares of ISCO Europe are expected to trade on the Deutsche Bourse independently of the company's shares in the US. ISCO Europe's shares will not be convertible into ISCO shares on any US exchange.

ISCO Europe will be licensed by ISCO to develop and market therapeutic products derived from ISCO's technology throughout the Euro Currency Countries and Switzerland. New technologies developed by either ISCO or ISCO Europe will be made mutually available, thus expanding the total funding available to ISCO worldwide without issuing new ISCO shares and enhancing the potential market and scientific development capacity of both companies.

It is expected that the new subsidiary will be funded initially by a private equity investment by ARG and that ARG will then assist in forming an investment group to invest up to $10 million concurrently with the listing of ISCO Europe on the Deutsche Bourse, the largest Securities Exchange in Europe. Following the financing of ISCO Europe, ISCO is expected to retain ownership of 80% or more of this new subsidiary.

'Although negotiations are still at the non-binding memorandum of understanding stage, this transaction, when completed, will expand ISCO's access to capital for worldwide expansion and ISCO's access to new scientific development without requiring equity dilution of ISCO's current shareholders. We are creating an investment, research and development, marketing and distribution entity by adding capital and human resources from Europe to help fulfill ISCO's goal of supplying its proprietary cells and cell therapies to the world,' said Kenneth Aldrich, Chairman and co-founder of ISCO.

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 most 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 of differing 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 on ISCO's website. 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 developments and therapeutic applications, the potential benefits of collaborations, affiliations, 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 forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Andrey Semechkin, Ph.D., CEO
aes@intlstemcell.com

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.