StemCell Therapy

LOS ANGELES (AP) The creation of California's stem cell agency in 2004 was greeted by scientists and patients as a turning point in a field mired in debates about the destruction of embryos and hampered by federal research restrictions.

The taxpayer-funded institute wielded the extraordinary power to dole out $3 billion in bond proceeds to fund embryonic stem cell work with an eye toward treatments for a host of crippling diseases. Midway through its mission, with several high-tech labs constructed, but little to show on the medicine front beyond basic research, the California Institute for Regenerative Medicine faces an uncertain future.

Is it still relevant nearly eight years later? And will it still exist when the money dries up?

The answers could depend once again on voters and whether they're willing to extend the life of the agency.

Several camps that support stem cell research think taxpayers should not pay another cent given the state's budget woes.

"It would be so wrong to ask Californians to pony up more money," said Marcy Darnovsky of the Center for Genetics and Society, a pro-stem cell research group that opposed Proposition 71, the state ballot initiative that formed CIRM.

Last December, CIRM's former chairman, Robert Klein, who used his fortune and political connections to create Prop 71, floated the possibility of another referendum.

CIRM leaders have shelved the idea of going back to voters for now, but may consider it down the road. The institute recently submitted a transition plan to Gov. Jerry Brown and the Legislature that assumes it will no longer be taxpayer-supported after the bond money runs out. CIRM is exploring creating a nonprofit version of itself and tapping other players to carry on its work.

"The goal is to keep the momentum going," board Chairman Jonathan Thomas said in an interview.

So far, CIRM has spent some $1.3 billion on infrastructure and research. At the current pace, it will earmark the last grants in 2016 or 2017. Since most are multi-year awards, it is expected to stay in business until 2021.

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California's stem cell agency ponders its future

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Stem cell researchers and institutions throughout the state are likely to be affected by proposed changes – to be discussed online publicly Tuesday – dealing with how the California stem cell agency will handle its $3 billion in grants.

An important online session – open to all interested parties – comes up then, but advance registration is required.

The proposals are wide-ranging and detailed. The nearly 500 recipients of CIRM grants should examine them closely in addition to any persons seriously interested in California stem cell affairs. The changes deal with such subjects as milestones for research grants, indirect costs, travel costs, withholding payments for failure to file a progress report and much, much more.

Here is a link to the main page for all this, which has instructions on how to register for the online session along with links to the changes and their rationale.

(Editor's note: This item was filed from the Rio Sabana in the Darien in Panama when we found a weak Internet cellular link. We are still underway so postings are unlikely between now and later this month.)

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

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

Stem cell researchers and institutions throughout the state are likely to be affected by proposed changes – to be discussed online publicly Tuesday – dealing with how the California stem cell agency will handle its $3 billion in grants.

An important online session – open to all interested parties – comes up then, but advance registration is required.

The proposals are wide-ranging and detailed. The nearly 500 recipients of CIRM grants should examine them closely in addition to any persons seriously interested in California stem cell affairs. The changes deal with such subjects as milestones for research grants, indirect costs, travel costs, withholding payments for failure to file a progress report and much, much more.

Here is a link to the main page for all this, which has instructions on how to register for the online session along with links to the changes and their rationale.

(Editor's note: This item was filed from the Rio Sabana in the Darien in Panama when we found a weak Internet cellular link. We are still underway so postings are unlikely between now and later this month.)

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

15-03-2012 18:22 A new pilot study is looking at ways to get organ transplant patient off immune suppressing drugs, and they're turning to stem cells to do it.

Read more:
On Call: Stem Cells Could Change Organ Transplants - Video

MONKEYS with Parkinson's disease-like symptoms have had their suffering eased by an injection of human embryonic stem cells (hESCs) into their brain.

Jun Takahashi of Kyoto University in Japan and colleagues injected these cells into monkeys whose brains had been damaged by a chemical that destroys dopamine-producing neurons and so causes Parkinson's symptoms.

Two monkeys received hESCs that had been matured into an early form of neural cell. Six months later, the monkeys had recovered 20 to 45 per cent of the movement they had lost before treatment. Post-mortems a year after treatment showed that the cells had developed into fully functioning dopamine-secreting neurons. Another monkey that received less-mature neural cells also showed improvements (Stem Cells, DOI: 10.1002/stem.1060).

"Monkeys starting with tremors and rigidity [began] to move smoothly, and animals originally confined to sitting down were able to walk around," says Takahashi.

The team says it will probably be four to six years before clinical trials in humans begin.

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Stem cell brain injections ease Parkinson's

17-03-2012 15:26 WARNING! BEWARE of this Hospital Angeles and especially DR. LOPEZ CORVALA who performs bariatric surgery like Lap Band, Gastric Bypass, Gastric Sleeve, Gastric Band in Cuidad Juarez, Mexico. He apparently has some control over the Stem Cell Regenerative Medicine Institute. I payed $25000 for stem cells to regenerate my liver cirrhosis. After NO IMPROVEMENT, he had the audacity to ask for $25000 more to repeat the surgery and treatment. I DO NOT RECOMMEND Dr. Lopez Corvala at the Hospital Angeles in Tijuana. PLEASE NOTE: email in video is incorrect. FEEL FREE TO EMAIL ME AT shamralaray@gmail.com.

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Hospital Angeles Tijuana Mexico Dr. Lopez Corvala LAP BAND and STEM CELLS Dr. Jesus Perez - Video

For about three days in January, Matt Ladd said he didnt know whether it was day or night, what was top or bottom.

I was probably as sick as Ive ever been, said Ladd, a Billings game warden, in a telephone interview from Seattle. As things got progressively worse and worse, I was really concerned about what was going on right then.

Ladd was headed to Seattle for stem cell bone marrow transplant surgery when an infection he was being treated for worsened. The infection started around a catheter inserted into his chest to deliver chemotherapy drugs. The chemo was battling Ladds acute myeloid leukemia and myelodysplastic syndrome, which was diagnosed in September. His bone marrow wasnt producing enough red blood cells.

The chemo worked. He was in remission and on his way to Seattle for a bone marrow transplant when the infection sent him into a rapid downward spiral. Because of the location of the catheter, the infection attacked his heart valves. During the struggle with the infection, his kidneys failed, his body retained water and he swelled up.

The infection scuttled plans for the bone marrow transplant surgery. With his kidneys failing, he had to undergo dialysis. As a final insult to his immune system, he had to take more chemotherapy since the surgery had been delayed and doctors feared the MDS might return.

My body and kidneys didnt respond well to the chemo, he said.

More than a month after he was scheduled to undergo surgery, Ladd is living in an apartment north of Seattle as family members rotate caretaking duties. His wife, Maureen, a math teacher at Billings West High, is holding down the fort at home, trying to maintain a sense of normalcy for their sons, Dylan, Logan and Jack.

What was going to be a short process has become a very long process, Maureen said.

Now the Ladds are waiting to hear whether Matt and his sister, Jessica Cook, will take part in a Seattle Cancer Center Alliance study of a new method of bone marrow transplantation. Since Ladds kidneys have been injured, he would normally have to have a reduced-intensity transplant used for the elderly and those with health issues, Maureen explained.

The experimental method would treat Cook, Ladds only sibling and a bone marrow transplant match, with Lipitor prior to the surgery. The cholesterol-lowering drug has shown promise in preventing reactions to transplants. If they are accepted for the study, it would mean a further delay of surgery, since Cook would have to be on the drug for a couple of weeks prior to the operation.

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Billings game warden fights cancer complications

13-03-2012 01:49 by:www.medicaltourism.hk

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China medical tourism--Brain Injury--stem cell therapy 1.flv - Video

A NEW stem cell therapy treatment to develop new bones for patients with bone loss and new skin for recipients of plastic surgery has been developed, doctors from Shanghai No.9 People's Hospital announced yesterday.

In the procedure, medical staff use a special machine to collect stem cells from a patient's blood. The stem cells adhere to a base made of a special biological material.

The stem cells are then transplanted into the patient's body, where they grow into either new bones or skin tissue, while the base is absorbed by the human body.

"So far the practice has been successful in treating patients with bone and skin loss," said Dr Dai Kerong from Shanghai Jiao Tong University's translational medicine institute at Shanghai No.9 hospital. "The stem cell technology will be used to develop corneas for blind people as well as treating heart attack and stroke patients by developing new heart and cerebral tissue."

The technology is patented in China and abroad and will be licensed within one or two years, according to Dai.

China has established 51 translational medicine centers to boost the introduction of laboratory research into clinical use.

The complicated procedures and documentation required often prevent doctors from introducing lab success into clinical practice.

Dai said one reagent developed by No. 9 hospital's doctors for in vitro fertilization received a license in Europe within six months and has been used in clinical practice "while this would take at least five years in China."

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Eastday-Big stem cell breakthrough

South Korean Hwang Woo Suk was long regarded as a cloning pioneer - until he was charged with having faked much of his stem cell research. Now, he is back with a new project: he wants to clone a woolly mammoth.

South Korean researcher and cloning pioneer Hwang Woo Suk hasn't been in the scientific spotlight ever since he claimed to have successfully created human embryonic stem cells by cloning six years ago, and that research turned out to be fake.

Now, the controversial veterinarian and researcher is in the headlines again. He wants to use frozen tissue samples to recreate an animal that last walked the earth some 10,000 years ago: a woolly mammoth.

Hwang Woo Su successfully cloned Snuppy in 2005

The scientist recently signed an accord to that effect with a university in Russia's Sakha Republic.

Vast areas of the republic are covered in permafrost that has begun to thaw over the years due to climate change, uncovering the well-preserved remains of several mammoths that had lain frozen in the ice for more than 10.000 years.

To clone new life from the remains, Hwang needs an intact cell nucleus that he hopes could contain the animal's entire genetic information. The scientist would then have to replace the nuclei of egg cells from a related species - in this case an Indian elephant - with those taken from the mammoth's cells.

It is possible - in principle. Three years ago, as part of a mammoth cloning project in Japan, researchers there managed to clone a mouse from the cells of a rodent that had been frozen for 16 years. Nothing has been heard of this project since then.

Fragmented DNA

Alex Greenwood, a biologist at the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, is skeptical about the mammoth-cloning project. A first look into the microscope may give scientists reason for hope because they can discern contours of cells and even cell nuclei in the mammoth tissue. But the structures are not intact, Greenwood said, "They are frozen imprints of ancient cells."

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Controversial scientist plans to clone a mammoth

Because everyones immune system is different, its impossible to predict with absolute certainty how any given person will react to a specific medication. In the not-too-distant future, however, at-risk patients may get their own custom-altered mouse, with an immune system thats a copy of their own. Medications could be tried out on the mouse first, and if it showed no adverse reactions, then the person could receive them. If the person had an autoimmune disease, the mouse could also provide valuable insight into its treatment. A team led by Columbia University Medical Centers Dr. Megan Sykes has recently developed a method of creating just such a personalized immune mouse.

The process begins by transplanting bone marrow stem cells from the human subject, along with a one-cubic-millimeter chunk of their thymus tissue, into a mouse with a disabled immune system. The thymus is an organ in the immune system, and the sample of it is implanted in the mouses kidney capsule, which is a thin membrane surrounding the kidney.

It incubates there for six to eight weeks, within which time it becomes seeded with the stem cells, which have been circulating in the mouses bloodstream. This in turn causes it to create a number of types of human immune cells, resulting in a robust and diverse human immune system matching that of the donor. Previous efforts have reportedly not been successful in creating a complete system, or have been hampered by the mice rejecting the human material.

Besides being used to test responses to medications, the personalized immune mice might also play a key role in developing individualized immunotherapies. These would allow patients to more successfully fight infections or cancer, or to accept transplanted tissue.

Additionally, Dr. Sykes plans on using the mice for research into type 1 diabetes, to determine how diabetic patients immune systems are different from those of non-diabetics, before the disease develops.

A paper on the research was recently published in the journal Science Translational Medicine.

Source: Columbia University Medical Center

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Peoples' immune systems can now be duplicated in mice

WASHINGTON (AP) -- Shares of Cytori Therapeutics Inc. jumped more than 10 percent Friday after the medical device maker said it received U.S. approval for a new version of its Puregraft system, which is used in cosmetic surgery.

Plastic surgeons use the device in fat grafting procedures that take fat from one part of the body and inject it into another. The device removes unwanted fluid, blood cells and debris from the fat and prepares it for grafting. Many procedures use fat from the thighs and abdomen to augment the breasts or face, aiming for a smoother, firmer look.

The latest version of the device can process 850 milligrams of fat, more than three times as much as the original Puregraft system approved in 2010. Plastic surgeons performed nearly 60,000 fat grafting procedures in the U.S. in 2010, according to industry figures

Shares of San Diego, Calif.-based Cytori rose 30 cents, or 10.6 percent, to close at $3.13.

Cytori has attracted attention from analysts for another device, called the Celution system, which some plastic surgeons have reportedly used to create fat grafts enhanced with adult stem cells. The device supposedly separates and purifies adult stem cells, which can then be mixed with fat grafts. Plastic surgeons in Los Angeles, Miami and elsewhere claim the so-called "stem cell facelift" creates a younger, healthier-looking physique than the incisions and implants associated with traditional surgery. But there are few studies to support such claims, and the Food and Drug Administration has not approved any therapies using stem cells for cosmetic use.

Early this year the two largest professional societies for plastic surgeons issued a joint statement calling on their members to avoid stem cell procedures. A review of the medical literature found little human data to support the benefits of injecting stem cells into patients, according to the statement from the American Society of Plastic Surgeons and the American Society for Aesthetic Plastic Surgery.

"The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence at this time," reads the joint statement, published in January.

"This is modern-day snake oil," said Dr. Felmont Eaves, president of the American Society of Plastic Surgeons, in an interview last year with the Associated Press. "It is the worst form of merchandising for a procedure that doesn't have scientific evidence to back it up."

Eaves pointed out that surgeons have been using fat grafts to plump up cheeks and breasts for decades. The practice has a mixed record of success, and has never eclipsed the more popular facelift and breast implant procedures.

"There's no evidence that going the extra step to create a stem cell version of this makes any difference," Eaves said.

Link:
Cytori rises on FDA clearance for fat graft device

A NEW stem cell therapy treatment to develop new bones for patients with bone loss and new skin for recipients of plastic surgery has been developed, doctors from Shanghai No.9 People's Hospital announced yesterday.

In the procedure, medical staff use a special machine to collect stem cells from a patient's blood. The stem cells adhere to a base made of a special biological material.

The stem cells are then transplanted into the patient's body, where they grow into either new bones or skin tissue, while the base is absorbed by the human body.

"So far the practice has been successful in treating patients with bone and skin loss," said Dr Dai Kerong from Shanghai Jiao Tong University's translational medicine institute at Shanghai No.9 hospital. "The stem cell technology will be used to develop corneas for blind people as well as treating heart attack and stroke patients by developing new heart and cerebral tissue."

The technology is patented in China and abroad and will be licensed within one or two years, according to Dai.

China has established 51 translational medicine centers to boost the introduction of laboratory research into clinical use.

The complicated procedures and documentation required often prevent doctors from introducing lab success into clinical practice.

Dai said one reagent developed by No. 9 hospital's doctors for in vitro fertilization received a license in Europe within six months and has been used in clinical practice "while this would take at least five years in China."

Read this article:
Eastday-Big stem cell breakthrough

14-03-2012 13:25 Could synthetic stem cells mean the end of certain forms of blindness? Scientists at the University of Wisconsin have created basic retina structures, giving hope to many with eye damage that their vision could be repaired someday. The retina structures were created by synthesizing stem cells from a patient's blood, and successfully sent important information to the brain that helps humans see. Scientists can create the stem cells from a simple blood test, and the ability to build the retina structures from the cells—and isolate which layers need repair—will allow researchers to further study degenerative diseases like retinitis pigmentosa. The study is still in its primordial phases, but it could lead to some big leaps forward in research and maybe even some day the ability to generate new cells for patients whose eyes are going bad. Just think: Someday grandma may stop asking you where she put her reading glasses!

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Scientists Make Big Leap in Eye Research by Growing Retina Structures - Video

The U.S. Food and Drug Administration has received a complaint alleging the Houston company involved in Gov. Rick Perry's unregulated adult stem-cell operation is a potential danger to patients and not in compliance with federal law.

In an eight-page letter sent last month, University of Minnesota bioethicist Leigh Turner called on the FDA to investigate Celltex Therapeutics Corp., which banks people's stem cells for future reinjection in the event of disease or injury. Perry was the company's first customer last year.

"It appears their business plan involves injecting or infusing on a for-profit, commercial basis non-FDA-approved adult stem cells into paying customers," Turner wrote in the Feb. 21 letter. "This plan conflicts with FDA regulations governing human stem cells."

An FDA spokeswoman declined comment, but Turner said an agency official told him the matter has been assigned to an investigator and is being taken seriously.

Celltex co-founder David Eller said Tuesday night he is confident the company will "meet all FDA specifications." He emphasized that Celltex doesn't administer stem cells, but stores and processes them at the behest of doctors who later reinject them into patients.

Dr. Stanley Jones, a Houston orthopedic surgeon, injected Perry's stem cells during his back surgery in July.

The plan by Celltex and Perry to make Texas a leader in the therapy have been controversial since details about the governor's procedure became known last summer. The therapy, drawing on the ability of adult stem cells to replenish dying cells, is promising but thought by most medical researchers to need much more clinical study before it is commercialized.

Stem cells are a kind of medicine known as biologics, therapy involving living cells rather than chemicals. Most medical experts say that adult stem-cell therapy involves more than the "minimal manipulation" the agency allows without its oversight because the cells are isolated, cultured in a laboratory and stored for some period of time before being reinjected.

The FDA has recently stepped up enforcement of unregulated adult stem cell activity, though legal experts interviewed last fall by the Chronicle said it was unclear whether the agency would look into Perry's procedure because he seemed fully informed and unharmed by it.

The Texas Medical Board is currently considering a policy that would require providers of stem cells and other experimental drugs to use them only with the permission of independent review committees that assess trials for patient safety. The policy comes up for final approval in April.

See the article here:
Gov. Perry's stem-cell firm draws FDA scrutiny

Todd Finkelmeyer has been covering higher education for the Capital Times since April 2008. He started contributing to the newspaper in 1990, was hired full-time in 1994 and has since covered everything from the Super Bowl to stem cell research. Follow his Campus Connection blog for the latest on higher education news in the Madison area.

Researchers working on the University of Wisconsin-Madison campus have found a way to use neurons derived from human embryonic stem cells to restore muscle coordination in mice inflicted with a Huntingtons disease-like condition.

The findings, which were reported Thursday in the journal Cell Stem Cell by a team of scientists who work at the university's Waisman Center, could one day help lead to new therapies for Huntington's disease, the debilitating disorder that affects both muscle coordination and cognitive ability. There currently are no effective treatments.

This is very exciting, and next well try to move onto different models, particularly in primates, to see whether this actually works in a larger brain, says Su-Chun Zhang, a UW-Madison neuroscientist and the senior author of the study.

Zhang, who specializes in producing different types of brain cells from stem cells, explains that this particular research focused on GABA neurons -- the cells that deteriorate and thus disrupt the brains circuitry that leads to the loss of motor function in patients with Huntington's. He notes the GABA neurons make a chemical that plays an important role in helping to link the communication network in the brain with movement.

Zhang and co-workers in the lab figured out how to produce large amounts of these GABA neurons from human embryonic stem cells, which they tested in mice with a Huntingtons-like ailment. Initially, the researchers were just trying to see whether or not these cells could safely integrate into the mouse brain. They were stunned to see that the cells not only successfully merged into the brain, but that they also eventually sent signals to the proper targets and rewired broken circuitry to restore motor functions.

This was quite surprising, says Zhang. These human neurons actually projected a long distance to another place in the brain and hooked up at the circuit, which is essential for our movement coordination. This is very critical, because in order for cell therapies to work for Huntingtons, the circuit has to be re-formed.

He notes scientists generally didnt believe it was possible for this circuitry to be rewired in older brains. In the mature brain, the nerve cells do not project a long distance, particularly into the correct target, Zhang explains. But that happened with these cells. So the point is, these stem cells somehow know where to go.

Its not clear how relevant this information will be in finding treatments for Huntingtons, but the UW-Madison scientists are hopeful their research can be used as another building block of information that can one day lead to treatments for the debilitating disease.

According to the Huntington's Disease Society of America, more than a quarter of a million Americans have the ailment or are at risk of inheriting the disease from an affected parent.

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Campus Connection: UW research hints at potential for Huntington’s treatment

Washington, Mar 16 (ANI): A special type of brain cell forged from stem cells could help restore the muscle coordination deficits that cause the uncontrollable spasms characteristic of Huntington's disease, a new study has suggested.

Huntington's disease, the debilitating congenital neurological disorder that progressively robs patients of muscle coordination and cognitive ability, is a condition without effective treatment, a slow death sentence.

"This is really something unexpected," said Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist and the senior author of the new study, which showed that locomotion could be restored in mice with a Huntington's-like condition.

Zhang is an expert at making different types of brain cells from human embryonic or induced pluripotent stem cells.

In the new study, his group focused on what are known as GABA neurons, cells whose degradation is responsible for disruption of a key neural circuit and loss of motor function in Huntington's patients.

GABA neurons, Zhang explained, produce a key neurotransmitter, a chemical that helps underpin the communication network in the brain that coordinates movement.

In the laboratory, Zhang and his colleagues at the UW-Madison Waisman Center have learned how to make large amounts of GABA neurons from human embryonic stem cells, which they sought to test in a mouse model of Huntington's disease.

The goal of the study, Zhang noted, was simply to see if the cells would safely integrate into the mouse brain.

To their astonishment, the cells not only integrated but also project to the right target and effectively re-established the broken communication network, restoring motor function.

The results of the study were surprising, Zhang explained, because GABA neurons reside in one part of the brain, the basal ganglia, which plays a key role in voluntary motor coordination.

Excerpt from:
'Forged' brain cells offers hope for Huntington's disease treatment

Newswise PHILADELPHIA Researchers at the Kimmel Cancer Center at Jefferson have demonstrated for the first time that the metabolic biomarker MCT4 directly links clinical outcomes with a new model of tumor metabolism that has patients feeding their cancer cells. Their findings were published online March 15 in Cell Cycle.

To validate the prognostic value of the biomarker, a research team led by Agnieszka K. Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology and Regenerative Medicine at Jefferson, analyzed samples of patients with triple negative breast cancer, one of the most deadly of breast cancers, with fast-growing tumors that often affect younger women.

A retrospective analysis of over 180 women revealed that high levels of the biomarker MCT4, or monocarboxylate transporter 4, were strictly correlated with a loss of caveolin-1 (Cav-1), a known marker of early tumor recurrence and metastasis in several cancers, including prostate and breast.

The whole idea is that MCT4 is a metabolic marker for a new model of tumor metabolism and that patients with this type of metabolism are feeding their cancer cells. It is lethal and resistant to current therapy, Dr. Lisanti said. The importance of this discovery is that MCT4, for the first time, directly links clinical outcome with tumor metabolism, allowing us to develop new more effective anti-cancer drugs.

Analyzing the human breast cancer samples, the team found that women with high levels of stromal MCT4 and a loss of stromal Cav-1 had poorer overall survival, consistent with a higher risk for recurrence and metastasis, and treatment failure.

Applying to a Triple Threat Today, no such markers are applied in care of triple negative breast cancer, and as a result, patients are all treated the same. Identifying patients who are at high risk of failing standard chemotherapy and poorer outcomes could help direct them sooner to clinical trials exploring new treatments, which could ultimately improve survival.

The idea is to combine these two biomarkers, and stratify this patient population to provide better personalized cancer care, said Dr. Witkiewicz

The findings suggest that when used in conjunction with the stromal Cav-1 biomarker, which the authors point out has been independently validated by six other groups worldwide, MCT4 can further stratify the intermediate-risk group into high and low risk.

Since MCT4 is a new druggable target, researchers also suggest that MCT4 inhibitors should be developed for treatment of aggressive breast cancers, and possibly other types. Targeting patients with an MCT4 inhibitor, or even simple antioxidants, may help treat high-risk patients, who otherwise may not respond positively to conventional treatment, the researchers suggest.

Paradigm Shift But the work stems beyond triple negative breast cancer, challenging an 85-year-old theory about cancer growth and progression.

See the article here:
Cancer Paradigm Shift: Biomarker Links Clinical Outcome with New Model of Lethal Tumor Metabolism