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Researchers reveal a chemo-resistant cancer stem cell as cancer's 'Achilles' heel'

Posted: September 10, 2012 at 11:16 pm

Public release date: 10-Sep-2012 [ | E-mail | Share ]

Contact: Mount Sinai Press Office newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Scientists at Mount Sinai School of Medicine have discovered a subpopulation of cells that display cancer stem cell properties and resistance to chemotherapy, and participate in tumor progression. This breakthrough could lead to the development of new tests for early cancer diagnosis, prognostic tests, and innovative therapeutic strategies, as reported in Cancer Cell.

Resistance to chemotherapy is a frequent and devastating phenomenon that occurs in cancer patients during certain treatments. Unfortunately, tumors that initially respond to chemotherapy eventually become resistant to it, contributing to tumor progression and death. The study reveals that these new cancer "stem" cells, which have not been differentiated into more specific cell types, are capable of multiplying despite being exposed to chemotherapy, while differentiated cells die.

Led by Carlos Cordon-Cardo, MD, PhD, Chair of Pathology, and Josep Domingo-Domenech, MD, PhD, Assistant Professor of Pathology at Mount Sinai, the research team generated cellular models of drug resistance by treating prostate tumor cell lines with increasing doses of the common chemotherapy drugs, including docetaxel. They identified a cell population expressing markers of embryonic development. In addition, these cells displayed cancer stem cell functions, including the capacity to initiate tumor cell growth. Next, the team evaluated human tissue samples of prostate cancer and found that patients with more aggressive or metastatic tumors had more of these cancer "stem" cells.

"This is the first time these so-called cancer stem cells of prostate have been identified as the basis for drug resistance and tumor progression, indicating that they are cancer's 'Achilles Heel,'" said Dr. Cordon-Cardo. "These findings are the culmination of more than six years of innovative research, which has led to the successful unveiling of cancer characteristics that are critical to understanding how the disease works and progresses."

The study also defines a new therapeutic strategy for patients with prostate cancer, consisting of a combination of standard chemotherapy and two pharmacological agents that inhibit key signaling pathways associated with embryonic development and cell differentiation. Results showed that chemotherapy eliminated differentiated tumor cells, whereas the signaling pathway inhibitors selectively depleted the cancer stem cell population. Some of these inhibitors are already in clinical trials, and some are FDA-approved.

"By targeting these newly identified cancer 'stem' cells, we are attacking the foundation of tumor growth, rather than treating the symptoms of it," said Dr. Domingo-Domenech. "The novel discovery of this cell population could lead to the development of new tests for early cancer diagnosis, prognostic tests, and innovative therapeutic strategies."

Ongoing studies suggest that this new cell type exist in other tumor types such as breast cancer, colon cancer, bladder cancer and lung cancer. Dr. Cordon-Cardo's team is studying these disease areas to determine the presence and impact of these cancer cells.

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Researchers reveal a chemo-resistant cancer stem cell as cancer's 'Achilles' heel'

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Soon a stem cell jabs to end wrinkles

Posted: September 10, 2012 at 1:10 pm

London, Sep 10:

Ladies, you may not have to depend upon painful Botox injections and expensive cosmetic surgery for long to look young.

A British firm is trialling a new natural method which involves injecting the patients own stem cells to restore skins youthful elasticity.

Researchers believe they will spur the growth of new skin cells, called fibroblasts, which make the elastic ingredient collagen which is produced in large quantities when we are young, but declines as we age, the Daily Mail reported.

The company Pharmacells, based in Glasgow, plans to begin clinical trials in 12 months, using stem cells harvested from a blood sample from the patients.

They believe the procedure could be commercially available in just three years, potentially revolutionising the market for anti-ageing treatments.

By using the bodys own cells, it is billed as a more natural approach to reducing the signs of ageing than Botox, a chemical which freezes the facial muscles to smooth wrinkles.

The company has licensed the technology to harvest a new type of stem cell called a blastomere-like stem cell (CORR) which is found circulating in the blood.

Like other types of stem cells, it is unspecialised and can develop into many other types of cell in the human body such as a liver, brain or skin cell.

The advantage of this particular one it is available in very large doses from one blood sample.

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Could this stem cell cure for wrinkles end the endless hunt for the perfect skin cream?

Posted: September 10, 2012 at 1:10 pm

British firm is trialling new method by injecting patient's own stem cells to restore skin's youthful elasticity

By Tamara Cohen

PUBLISHED: 10:40 EST, 9 September 2012 | UPDATED: 02:12 EST, 10 September 2012

Scientists will begin clinical trials in 12 months, using stem cells harvested from a blood sample from the patients

Scientists are working on a new weapon in the war against wrinkles.

There are not many things women have not tried in the quest for a youthful complexion from lotions and potions to Botox and cosmetic surgery.

But a British firm is trialling a new method which involves injecting the patients own stem cells to restore skins youthful elasticity.

Researchers believe they will spur the growth of new skin cells, called fibroblasts, which make the elastic ingredient collagen which is produced in large quantities when we are young, but declines as we age.

The company Pharmacells, based in Glasgow, plan to begin clinical trials in 12 months, using stem cells harvested from a blood sample from the patients.

They believe the procedure could be commercially available in just three years, potentially revolutionising the market for anti-ageing treatments.

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A New Approach to Erectile Dysfunction? Study Shows Adult Stem Cells Offer Hope to Patients with Erectile Dysfunction …

Posted: September 10, 2012 at 1:10 pm

SEOUL, South Korea, Sept. 10, 2012 /PRNewswire/ -- After more than a decade of short-term cures to erectile dysfunction, most aimed at symptoms rather than the underlying issues of nerve damage, a new approach has emerged from adult stem cell technology developed by RNL Bio. Dr. Ji Youl Lee and the RNL Stem Cell Technology Institute (RNL SCTI) team, working at St. Mary's Hospital in Seoul, found in animal studies that adipose (fat) derived adult human stem cells, grown in culture, were very effective in treating cavernous nerve injury. When rats with cavernous nerve injury, the equivalent of erectile dysfunction (ED) in humans, were treated with RNL Bio's patented adult stem cells, they showed significant recovery of nerve system capacity and long-term recovery. The RNL SCTI team has significant evidence now to suggest that similar, long-term recovery is around the corner for men suffering from recurrent ED and the underlying damage to the nerves in the male reproductive system.

The study, "Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury," is published in the current issue of the Journal of Sexual Medicine (JSM), among the top 10% most-cited journals in Urology,* and the Official Journal of the International Society for Sexual Medicine. JSM, published by Wiley, the world's largest medical journal publisher, is a peer-reviewed journal whose mission is to publish the best new research in biomedical approaches to pathologies of human sexuality. The study was also released ahead of print as an ePub by the Editors. [PMID: 22642440: http://www.ncbi.nlm.nih.gov/pubmed/22642440%5D

Potential therapies from adult stem cells could benefit many men who have cancer of the prostate gland. Prostate cancer is the most common cancer and second leading cause of death in USA, and an increasingly common disease in many other nations (including Korea, where it is now the fifth most prevalent form of cancer). Among the most common treatments for prostate cancer is prostatectomy. The main cause of cavernous nerve injury is prostatectomy, and 20 to 70% patients who undergo prostatectomy experience ED, despite recent development of robotic and laparoscopic operation. Researchers searching for ways to prevent nerve injury have begun to focus on regenerating damaged nerves. So, Dr. Lee's team turned to adult stem cells. His team injected adipose-derived adult stem cells and porous membrane for releasing growth factors and regenerating nerves into rats with cavernous nerve injury. His team identified that stem cells increase the internal pressure of subjects' cavernous tissue at a statistically significant level.

Dr. Jeong-Chan Ra, president of RNL Stem Cell Technology Institute, noted that "patients' own adipose derived stem cells are expected to play a crucial role in therapy for ED in the near future, and to go beyond the limitations of current therapy, including its side effects."

* Journal Citation Reports: Thomson/Reuters, 2010/11

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A New Approach to Erectile Dysfunction? Study Shows Adult Stem Cells Offer Hope to Patients with Erectile Dysfunction ...

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Arroyo undergoes 4th stem cell treatment

Posted: September 9, 2012 at 8:16 pm

By Leila B. Salaverria Philippine Daily Inquirer

Former President and now Pampanga Rep. Gloria Macapagal Arroyo: Stem cell treatment

MANILA, PhilippinesLike her predecessor, former President and Pampanga lawmaker Gloria Macapagal Arroyo has turned to stem cell therapy in an effort to improve her health.

Arroyo said in her official Twitter account that she would have her fourth stem cell intravenous treatment with her alternative medicine doctor on Monday.

Arroyo said her treatment would involve cultured stem cells, and it would be much more modest in price than the one coming from sheep or ones own body.

A close friend and ally of Arroyo, Quezon Representative Danilo Suarez, confirmed that the President has started stem cell therapy, and that she told him that the stem cells she has been using did not come from lamb placenta, and was the less costly form of stem cell treatment.

If you have a lot of health problems, you will try such things, Suarez said on Sunday.

Suarez said he has even filed a resolution to investigate the practice of stem cell treatments in the country, as well as the claims being made about it, considering that it has been gaining popularity.

The public needs to be better informed about it. It might have setbacks that we need to know about, he said.

The therapy involves the use of fresh cells, which are injected into the body to regenerate cells to treat illnesses or reverse aging.

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StemCells, Inc., Gunning for Another $10 Million from California Stem Cell Agency

Posted: September 9, 2012 at 3:58 pm


Fresh from winning $40 million from the
California stem cell agency, StemCells, Inc., is shooting for
another, $10 million award from the state research effort.

The latest proposal comes as the
publicly traded firm also faces the task of raising $40 million that it
has promised the agency to match the earlier awards. That figure
could well rise to $50 million given the new application.
Martin McGlynn, CEO of the
well-connected Newark, Ca., firm, disclosed StemCells, Inc.'s,
latest proposal in an article by Catherine Shaffer in BioWorld. She
wrote,

“Already looking ahead, StemCells has
set its sights on one more CIRM initiative designed to fund early
stage clinical trials over a four-year period. StemCells has applied
for that grant, worth up to $10 million, to fund a Phase II trial in
PMD(Pelizaeus-Merzbacher disease).”

The article did not disclose the timing on the new application.
StemCells, Inc.'s lobbying efforts with the stem cell agency were vigorously aided by the former chairman of the $3 billion
California stem cell agency, Robert Klein (see here and here). And Wednesday evening, the company convinced
the state agency's board to overturn two successive reviewer rejections of a
$20 million proposal for Alzheimer's research. The vote was 7-5.
Klein's efforts came in a record-breaking round of appeals and emotional presentations by patient advocates, which triggered complaints from the board this week about "arm-twisting" and politicking. 
StemCells, Inc., was founded by the
eminent Stanford stem cell researcher Irv Weissman, who helped to
raise millions for the ballot initiative that created the stem cell
agency. He additionally appeared in in the campaign's TV advertising.
The campaign was headed by Klein, who ultimately raised $35 million
to convince voters to create the agency. Weissman is currently on the board
of the StemCells, Inc. His wife is executive vice president.
In July, the stem cell agency board
approved the first $20 million award to the firm for research involving spinal injury.
McGlynn told BioWorld,

"We're the only company that has
programs going on in all three regions of the central nervous system:
the brain, the spinal cord and the eye."

Not discussed in the BioWorld article
was a requirement, imposed by the CIRM board, that StemCells, Inc.,
show it can deliver $20 million in matching funds on the Alzheimer's
award before receiving any state funds. CIRM said no such board
requirement existed on the spinal award, but the firm has promised to
match the $20 million on that award as well.
BioWorld described the awards as
grants. In fact, they are loans. But under the terms of the loans, if
the research is not successfully commercialized, it will be
forgiven.  

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

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Arm-twisting and Emotion: Stem Cell Directors Move to Reform Appeals on Multimillon Dollar Grants

Posted: September 9, 2012 at 3:58 pm


Frustrated with politicking,
“arm-twisting,” lobbying and “emotionally charged
presentations,” the governing board of the $3 billion California
stem cell agency today approved short-term changes in its grant
appeal process and ordered up a study to prepare long-term reforms.

The moves followed a prolonged series of appeals on grant applications that began in July and continued through today,
setting records for the number of appeals and generating hours of
sometimes tearful and emotion-laden presentations from members of the
public.
The board adopted changes in the appeal process for its next few meetings that are aimed at curbing its
free-wheeling nature and making it more understandable to the public
and applicants. The board also directed creation of a panel to make
recommendations by the end of the year for more wide-ranging reforms.
Directors of the agency were clearly
not happy with the appeal process this summer. However, it has been a
problem since 2008 when Bert Lubin, now a director of the stem cell
agency and CEO of Childrens Hospital of Oakland, Ca., was the first applicant to make a public pitch before the board to overturn
reviewer rejection of his application.
One director, UCLA medical school dean,
Gerald Levey, said at the time,

"I don't think we can run a board
this way. If we do, it would be chaos." 

Today, CIRM Director Carmen Puliafito,
dean of the USC School of Medicine, said that “lots of lobbying”
was going over the last couple of months. He predicted there will
more lobbying and “more politicking.” Puliafito said,

“On big money grants, people will be
calling their friends.”

The name of former board chairman,
Robert Klein, was not mentioned during this afternoon's discussion.
But Klein vigorously and successfully backed an appeal (see here,
here and here) by StemCells, Inc., of Newark, Ca., for a $20 million
application that had been rejected twice by reviewers. Last night the
board approved the award on a 7-5 vote. It was the first time the
board has approved an award that was rejected twice by its reviewers.
Director Jeff Sheehy, co-vice chairman
of the review group and a communications manager at UC San Francisco,
said the agency is dealing with “big money grants” that are
“incredibly complex.” He also referred to “certain arm-twisting
by certain individuals.”
Several board members made references
to appearances by persons who have diseases or conditions that might
be affected by CIRM-financed research. Director Duane Roth, head of
CONNECT, a San Diego business development organization, said the
board is making decisions in “an emotionally charged setting.”
Other issues cited by directors include
the integrity of review process, fairness, consistency, shifting
appeals procedures, transparency and board discipline on appeals.

James Harrison, outside counsel to the board, said the board's action today includes "eliminating the reference to unpublished data in the discussion of 'material new information," imposing a 3-page limit on other correspondence, explaining that applicants should have seven business days from the time the (grants review group) recommendation is made available to them to file an (extraordinary petition), and posting all of the information regarding these policies in one place on CIRM’s website."

For a list of articles and CIRM
documents dealing with the appeal process, see here.

Source:
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Florida Researcher Wins $6.7 Million Grant to Come to Golden State

Posted: September 9, 2012 at 3:58 pm


Dennis Steindler
UF Photo

The governing board of the California stem cell agency this morning approved a $6.7 million grant to recruit Dennis Steindler of the University of Florida to the Parkinson's Institute in Sunnyvale, Ca.

The grant was approved immediately following a 45-minute executive session with no further debate. (For more on this, see here, here and here.)

Steindler later told the California Stem Cell Report he would begin work in California as soon as possible.

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California Stem Cell Agency Okays $38 Million for Basic Research

Posted: September 9, 2012 at 3:58 pm


Directors of the California stem cell agency today approved about $38 million for research into basic biology, including two appeals by researchers on applications initially rejected by reviewers.

The governing board turned down five appeals in the round, which attracted 357 applications in its "pre-app" process, 64 of which were invited to apply. Reviewers approved 25 applications.

The following appeals in the biology round were approved:

  • $1.3 million, Deborah Lieu of UC Davis. (Review summary here, appeal here.) 764
  • $1.4 million, Yanhong Shi  of the City of Hope. (See review summary here and appeal here.)

The board also approved another application that was rejected by reviewers based on a recommendation by CIRM President Alan Trounson.  It is very unusual for the board to approve rejected applications based on staff recommendations following a review. Trounson described the grant addressed a major bottleneck in stem cell science.

 The California stem cell agency is expected to post a press release shortly with the names of all recipients. The agency usually withholds names of applicants until the the board formally acts.
(An earlier version of this item reported that the board approved $37 million in grants.)

Source:
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Board Concludes Private Session on Recruitment Grant

Posted: September 9, 2012 at 3:58 pm


The governing board of the California stem cell agency has just concluded a 45 minute executive session on a $6.7 million grant to recruit a Florida scientist to the Parkinson's Institute in Sunnyvale, Ca.

It was the longest executive session ever on a recruitment grant, which are usually approved routinely with little serious discussion.

The board is now resuming discussion of the matter(see here and here.)

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