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."

The following is an excerpt from the June 29, 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

Q&A with ISCO



International Stem Cell Corp. (OTCBB: ISCO) has also been the target of rumor campaigns. ISCO, incidentally, recently announced further positive IP news. Specifically, Advanced Cell Technology, Inc. (ACT) was just issued U.S. Patent Number 7736896 covering a method for producing retinal pigment epithelial cells. ISCO, however, had previously acquired rights to this technology from ACT, so the award solidifies their position in stem cell eye therapies.

ISCO's corneal research also got an unexpected boost last week, though it's not clear how many people know it yet. A stem cell breakthrough from Italy made quite a few headlines. The article that provoked the coverage was in the June 23 online version of The New England Journal of Medicine (NEJM). Specifically, it featured clinical research from professor Graziella Pellegrini et al. titled "Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration." A helpful video by ABC News can be viewed here.



The coverage of the journal article is, however, incomplete. So let me put it in perspective.

The procedure made use of the well-established practice of extracting and cultivating limbal stem cells. Each of the patients, in effect, had stem cells removed from at least one eye. Once the adult stem cells were multiplied in the lab, they were applied to the cornea. There, they regenerated the corneal epithelium (the outermost thin layer of the cornea), restoring sight.

This is wonderful proof of the power of stem cells, but it doesn't represent a breakthrough in terms of basic science or investment possibilities. This is because the cost of extracting these surviving stem cells is very high. So is multiplying and reattaching them. The only reason the experiments were even allowed to proceed is that all the cell materials come from the subjects of the procedures. They would not have been allowed if, for example, scientists wanted to use the stem cells from one patient to treat another patient. Nor is it clear to what extent, if any, a company can patent these procedures.

On the other hand, the Italian procedures were most successful when they were combined with the implantation of replacement corneal structures. Those replacement corneas cannot be regenerated from limbal stem cells. In fact, they came from cadavers.

ISCO, however, is now able to grow them in the lab to produce cheaper, safer corneas. ISCO is involved in discussions with various companies to commercialize those parthenogenic corneal structures.

For most patients, who have enough of their own stem cells to regenerate the corneal epithelium, ISCO's corneas are all that are required to recover sight. Eventually, in fact, I suspect that ISCO will also have off-the-shelf limbal stem cells that will regenerate the corneal epithelial too. These cells would be from each of ISCO's cell bank lines. Now being established, it will include 50-100 cell lines that immune match most of the world's population. No other company has this ability to provide inexpensive stem cells for the masses.

Now allow me to debunk some of the rumors currently being spread about ISCO. Normally, as you know, I don't like to dignify these attacks, but I do make exceptions when it's important. I'm doing this, by the way, in a question-and-answer format that board chairman Ken Aldrich was kind enough to answer. The questions deal with some of the unfounded rumors circulating. If these don't concern you, feel free to skip them. Q1. Did ISCO close its financing?



A1. Yes, they did a $10 million financing, and then used $2.5 million as part of a balance sheet cleanup that removed approximately $15 million of 10% preferred stock and still left them with an additional $7.5 million in cash on the balance sheet, in addition to whatever cash was already there.

Q2. Doesn't Socius hold a lot of preferred stock that will be a future burden to ISCO?



A2. No, all of that has been retired as part of the capital restructuring announced in an 8-K filed June 11, 2010. As a result, Socius and its predecessor company, Optimus, hold no preferred shares of ISCO at all.

Q3. Is the company running out of money?



A3. Based on the monthly "burn" rate of about $550,000 for the last 15 months ($562,000 for the last quarter), the proceeds of the company's most recent financing of $7.5 million after the repayment of the outstanding preferred stock of Socius and Optimus would give the company at least 12 months of "runway," even without any additional revenues from operations, licensing or partnerships.



I could go on, but this is pretty long. Next week, I'll have more updates.

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.

It turns out that not all the hairlike cilia projecting from the surfaces of many cells in the human body are equal--there are the myriad ones for sweeping, swimming and other functions, and then there is the until recently mysterious primary cilium.

Nearly all human cells contain these numerous microscopic projections. The more abundant variety of cilia are motile; they act like oars, paddling in coordinated waves to help propel cells through fluid, or to sweep material across cellular surfaces (as in the respiratory system, where millions of cilia lining the airways help to expel mucus, dead cells and other bodily debris). By contrast, cells also contain a single, nonmotile cilium known as the primary cilium. Its presence on cells has been known for more than a century, but many believed it was a functionless evolutionary remnant.

[More]

Cell - Biology - Cell biology - Cilium - Human body

For those of you who like stories with simple plots and tidy endings, I must confess the tale of the Human Genome Project isn't one of those. The story didn't reach its conclusion when we unveiled the first draft of the human genetic blueprint at the White House on June 26, 2000. Nor did it end on April 14, 2003, with the completion of a finished, reference sequence. [More]

Human Genome Project - White House - Biology - genetic - Francis Collins

Jeffrey Janus serves as director and senior vice president of operations of new CHI member International Stem Cell Corp. and president and chief executive officer of Lifeline Cell Technology, one of the company’s subsidiaries. International Stem Cell Corp. (ISCO.OB) is a publicly traded stem cell therapy company with research and manufacturing facilities in Oceanside, Calif., and Walkersville, Md. The company’s technology revolves around its discovery of a proprietary and unique class of stem cells called human parthenogenetic stem cells (hpSC). These cells have distinct medical, practical and ethical advantages over embryonic and adult stem cells. They allow immune-matched stem cells and therapeutic cells to be “banked” and available immediately for millions of patients who are in critical need and cannot wait to derive cells from their own bodies. In addition to Lifeline Cell Technology, the company has another subsidiary called Lifeline Skin Care.

Janus is trained in biochemistry and business management and has more than 20 years experience focused on cell-based businesses. He is a member of the team that discovered parthenogenesis and is published in the stem cell field. After joining International Stem Cell Corp., (ISCO) Janus subsequently founded Lifeline Cell Technology to meet a growing need for media and human cells in pharmaceutical drug screening, consumer product testing and basic research at universities and government laboratories and to provide revenue and operational infrastructure for ISCO. The CHI Blog recently caught up with Janus to find out the latest on the company.

Q: How did your company get started? A: We started this company based on the work of Elena Revazova, M.D., Ph.D., a scientist well known in Russia who had a dream of curing diabetes using embryonic stem cells. She came to the United States to work and her talent and expertise in growing human cells was discovered by ISCO’s founders, who decided to form a company around her knowledge and skill. At the time, U.S. President [George W.] Bush was restricting the use of embryonic stem cells on ethical grounds, and there were also patent issues around embryonic stem cells, as there still are. We recognized that the ethical issue was important, but medially the most important problem with stem cell therapy was likely to be immune rejection. We realized we could address these issues by developing the technology called parthenogenesis and mitigate delays from funding and restrictions by working in Russia. So Dr. Revazova went back to Russia, and we set up a collaboration in Moscow to begin her work with parthenogenesis. Today our company has all of the intellectual property rights to parthenogenesis, a very powerful technology. We have also recently brought in Andrey Semechkin, Ph.D. as our CEO. Dr. Semechkin is a well-known scientist in the field of systems analysis and an accomplished businessman.

Q: How does parthenogenesis work? A: It’s the derivation of stem cells from an unfertilized human egg. The ethical issue surrounding work with embryonic stem cells is caused by the fact that embryonic stem cells are derived from a fertilized embryo, which has the potential to be a human being. However, if you do not fertilize the egg and yet you can derive stem cells from it that are functional, you’re not destroying a viable human embryo—and that’s exactly what Dr. Revazova did. We perfected parthenogenesis and brought it back to the United States. As a result, we have been able to overcome the ethical issue surrounding using embryonic stem cells with parthenogenesis.

Q: What are your technology’s other advantages? A: Parthenogenesis makes embryonic stem cells (or what we call parthenogenetic stem cells) that can be immune matched to millions of people. Using embryonic stem cells, the way they are currently made, is sort of like trying to do a bone marrow transplant between one person and another picked at random without making sure you have a match. If someone needs to have a bone marrow transplant, they usually go to brothers or sisters first and try to do an immune match. For a different set of reasons a similar situation exists with blood transfusions, although type O blood can be given to almost everyone. Our cells are similar in that the parthenogenic stem cells can be immune matched to many people, and that’s the unique quality of our cells.

Q: What are the biggest opportunities for your business going forward? A: We are creating a bank of hpSC that are “pluripotent” and carry common immune types that will match a large percent of the U.S. population, and this is a huge opportunity. These will be clinical grade and will be made in our new manufacturing facility located in Oceanside, Calif. Our biggest opportunity is the potential ability of our stem cells to be universally utilized for therapy. Scientists across the world are working on embryonic stem cells and figuring out ways to make therapeutic cells such as liver cells or nerve cells for a whole host of diseases. Eventually these therapies will need a cell or process that will minimize immune rejection. Our cells can be immune matched to millions of persons and are thus a solution for this need. So in a way, much of the work that’s going on right now across the world with embryonic stem cells accrues to our benefit. In addition, we are focused in four distinct areas—diabetes, liver disease, retinal and corneal disease, and nerve disease. We are currently growing cells to cure corneal blindness and have actually grown cornea tissue. We’re working with the University of California, Irvine to grow cells with a retina for macular degeneration. We have grown cells that are very similar to liver cells that are also related to a cell type called beta cells, which may be useful for diabetes. Collaborations with companies and universities present strong opportunities, and we’ve collaborated with Novocell in San Diego to further our work with diabetes, and we’re collaborating with UC San Francisco to test our liver cells derived from our parthenogenic stem cells and with researchers in Germany to study nerve cells generated from our stem cells.

Q: Tell us a little bit about your subsidiaries. A: One unique thing about our company is that we are a research-oriented biotech company that actually has income. One of our subsidiaries, Lifeline Cell Technology, is growing very nicely (with a 150 percent increase in sales over the last year) by selling research products to grow human cells and study human disease. Lifeline has more than 70 products and will be releasing more than a dozen more in 2010. Lifeline Skin Care was created in 2009 based on our discovery that derivatives from our parthenogenetic stem cell technology have proven to be beneficial to human skin. Lifeline Skin Care is developing several products and is beginning early-stage clinical trials with these skin products. We anticipate that these skin care products will help to generate income and fund our continuing stem cell therapeutic research.

Q: What are your company’s greatest accomplishments so far? A. We have successfully created 10 human parthenogenetic stem cell lines, one which carries the most common immune type in the United States and matches over a hundred million persons across the world. We are a fast-growing company with more than 12 scientists working in various areas of therapy and product development. Our stem cells have proven to be able to create cells that may be useful in therapy, including liver-like cells, corneal cells, retinal cells, nerve cells and cell types that may ultimately be useful in the treatment of diabetes. We have set up collaborations with major universities and researchers across the world. The amazing thing about our company is that we have developed into a company that has manufacturing, products, sales, quality control, therapeutic research, and an accounting department in such a short time. We have all the workings of a fully functional product manufacturing and therapeutic research company. It amazes me that we are making sales, whereas most companies our size are basic research and development companies. We know how to make human cells and freeze, store and manipulate them so that they are clinical grade. I think our technology, our knowledge of cell culture and our ability to manufacture are three very strong reasons that we have been successful.

CHI-Advancing California biomedical research and innovation
SOURCE: http://californiahealthcareinstitute.blogspot.com/2010/02/executive-spotlight-jeffrey-janus.html

The first discovery of a cancer gene marker--the BRAF oncogene for melanoma and colorectal malignancies--back in 2002 changed the way many researchers thought about cancer treatment. Rather than approach the disease based on what region of the body it stemmed from, scientists began to identify cancers in terms of their genetic signatures. Researchers now recognize more than 200 kinds of cancer--all genetically unique. [More]

Cancer - Health - Conditions and Diseases - Colorectal cancer - Management of cancer