Breast cancer

CIRM Board Approves New Clinical Trial for Breast Cancer Related Brain Metastases

/ Yimy Villa / Leave a comment
Dr. Saul Priceman

Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $9.28 million to Dr. Saul Priceman at City of Hope to conduct a clinical trial for the treatment of breast cancer related brain metastases, which are tumors in the brain that have spread from the original site of the breast cancer.

This award brings the total number of CIRM-funded clinical trials to 56. 

Breast cancer is the second-most common cancer in women, both in the United States (US) and worldwide.  It is estimated that over 260,000 women in the US will be diagnosed with breast cancer in 2019 and 1 out of 8 women in the US will get breast cancer at some point during her lifetime. Some types of breast cancer have a high likelihood of metastasizing to the brain.  When that happens, there are few treatment options, leading to a poor prognosis and poor quality of life. 

Dr. Priceman’s clinical trial is testing a therapy to treat brain metastases that came from breast cancers expressing high levels of a protein called HER2.   The therapy consists of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells.  The T cells are modified with a protein called a chimeric antigen receptor (CAR) that recognizes the tumor protein HER2.  These modified T cells (CAR-T cells) are then infused into the patient’s brain where they are expected to detect and destroy the HER2-expressing tumors in the brain.

CIRM has also funded the earlier work related to this study, which was critical in preparing the therapy for Food and Drug Administration (FDA) approval for permission to start a clinical trial in people.

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news,” says Maria T. Millan, M.D., the President and CEO of CIRM.  “There are few options for patients with breast cancer brain metastases.  Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

The CIRM Board also approved investing $19.7 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Dr. Mark Tuszynski at the University of California San Diego (UCSD) was awarded $6.23 million to develop a therapy for spinal cord injury (SCI). Dr. Tuszynski will use human embryonic stem cells (hESCs) to create neural stem cells (NSCs) which will then be grafted at the injury site.  In preclinical studies, the NSCs have been shown to help create a kind of relay at the injury site, restoring communication between the brain and spinal cord and re-establishing muscle control and movement.

Dr. Mark Humayun at the University of Southern California (USC) was awarded $3.73 million to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD), the leading cause of vision loss in the US.

The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dry AMD, supporting the survival of photoreceptors in the affected retina, the kind of cells damaged by the disease.

The TRAN1 awards went to:

Stay tuned for our next blog which will dive into each of these awards in much more detail.

Developing a non-toxic approach to bone-crushing cancers

/ Kevin McCormack / Leave a comment
When cancer spreads to the bone the results can be devastating

Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.

Bone metastasis – where cancer starts in one part of the body, say the breast, but spreads to the bones – is one of the most common complications of cancer. It can often result in severe pain, increased risk of fractures and compression of the spine. Tackling them is difficult because some cancer cells can alter the environment around bone, accelerating the destruction of healthy bone cells, and that in turn creates growth factors that stimulate the growth of the cancer. It is a vicious cycle where one problem fuels the other.

Now researchers at UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with targeting agents. These act like a drug delivery device, offloading different agents that simultaneously attack the cancer but protect the bone.

Weian Zhao; photo courtesy UC Irvine

In a news release Weian Zhao, lead author of the study, said:

“What’s powerful about this strategy is that we deliver a combination of both anti-tumor and anti-bone resorption agents so we can effectively block the vicious circle between cancers and their bone niche. This is a safe and almost nontoxic treatment compared to chemotherapy, which often leaves patients with lifelong issues.”

The research, published in the journal EBioMedicine, has already been shown to be effective in mice. Next, they hope to be able to do the safety tests to enable them to apply to the Food and Drug Administration for permission to test it in people.

The team say if this approach proves effective it might also be used to help treat other bone-related diseases such as osteoporosis and multiple myeloma.

A cancer therapy developed at a CIRM Alpha Stem Cell Clinic tests its legs against breast cancer

/ Pallavi Penumetcha / 1 Comment

Breast cancer cells

Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein on the cell surface membrane stained green. Image courtesy The National Institutes of Health

A Phase 1 clinical trial co-sponsored by CIRM and Oncternal Therapeutics, has started treating patients at UC San Diego (UCSD). The goal of the trial is to test the safety and anti-tumor activity of the Oncternal-developed drug, cirmtuzumab, in treating breast cancer.

Breast cancer is the second most common cancer to occur in women, regardless of race or ethnicity. More than 260,000 new cases are expected to be diagnosed this year in the United States alone. Typically, breast cancer cases are treated by a combination of surgery to remove the tumor locally, followed by some kind of systemic treatment, like chemotherapy, which can eliminate cancer cells in other parts of the body. In certain cases, however, surgery might not be a feasible option. Cirmtuzumab may be a viable option for these patients.

The drug acts by binding to a protein called ROR1, which is highly abundant on the surface of cancer cells. By blocking the protein Cirmtuzumab is able to promote cell death, stopping the cancer from spreading around the body.

Because ROR1 is also found on the surface of healthy cells there were concerns using cirmtuzumab could lead to damage to healthy tissue. However, a previous study revealed that using this kind of approach, at least in a healthy non-human primate model did not lead to any adverse clinical symptoms. Therefore, this protein is a viable target for cancer treatment and is particularly promising because it is a marker of many different types of cancers including leukemia, lung cancer and breast cancer.

Phase 1 clinical trials generally enroll a small number of patients who have do not have other treatment options. The primary goals are to determine if this approach is safe, if it causes any serious side-effects, what is the best dosage of the drug and how the drug works in the body. This clinical trial will enroll up to 15 patients who will receive cirmtuzumab in combination with paclitaxel (Taxol), a vetted chemotherapy drug, for six months.

Earlier this year, a similar clinical trial at UCSD began to test the effectiveness a of cirmtuzumab-based combination therapy to treat patients with B-cell cancers such as chronic lymphocytic leukemia. This trial was also partially funded by CIRM.

In a press release, Dr. Barbara Parker, the co-lead on this study states:

“Our primary objective, of course, is to determine whether the drug combination is safe and tolerable and to measure its anti-tumor activity. If it proves safe and shows effectiveness against breast cancer, we can progress to subsequent trials to determine how best to use the drug combination.”

Stem Cell Roundup: Protein shows promise in treating deadliest form of breast cancer: mosquito spit primes our body for disease

/ Kevin McCormack / 1 Comment

Triple negative breast cancerTriple negative breast cancer is more aggressive and difficult to treat than other forms of the disease and, as a result, is more likely to spread throughout the body and to recur after treatment. Now a team at the University of Southern California have identified a protein that could help change that.

The research, published in the journal Nature Communications, showed that a protein called TAK1 allows cancer cells from the tumor to migrate to the lungs and then form new tumors which can spread throughout the body. There is already an FDA-approved drug called OXO that has been shown to block TAK1, but this does not survive in the blood so it’s hard to deliver to the lungs.

The USC team found a way of using nanoparticles, essentially a tiny delivery system, to take OXO and carry it to the lungs to attack the cancer cells and stop them spreading.

triple_negative_breast_cancer_particle_graphic-768x651In a news release Min Yu, the principal investigator on the team, said that although this has only been tested in mice the results are encouraging:

“For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic. So, nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis.”

Mosquito spit and your immune system

Mosquito

Mosquito bite: Photo courtesy National Academy of Sciences

Anyone who has ever been bitten by a mosquito knows that it can be itchy and irritable for hours afterwards. But now scientists say the impact of that bite can last for much longer, days in fact, and even help prime your body for disease.

The scientists say that every time a mosquito bites you they inject saliva into the bite to keep the blood flowing freely. But that saliva also has an impact on your immune system, leaving it more vulnerable to diseases like malaria.

OK, so that’s fascinating, and really quite disgusting, but what does it have to do with stem cells? Well, researchers at the National Institute of Health’s (NIH) Malaria and Vector Research Laboratory in Phnom Penh, Cambodia engrafted human stem cells into mice to study the problem.

They found that mice with the human stem cells developed more severe symptoms of dengue fever if they were bitten by a mosquito than if they were just injected with dengue fever.

In an article in Popular Science Jessica Manning, an infectious disease expert at the NIH, said previously we had no idea that mosquito spit had such a big impact on us:

“The virus present in that mosquito’s saliva, it’s like a Trojan horse. Your body is distracted by the saliva [and] having an allergic reaction when really it should be having an antiviral reaction and fighting against the virus. Your body is unwittingly helping the virus establish infection because your immune system is sending in new waves of cells that this virus is able to infect.”

The good news is that if we can develop a vaccine against the saliva we may be able to protect people against malaria, dengue fever, Zika and other mosquito-borne diseases.

Stem cell study holds out promise for kidney disease

/ Kevin McCormack / 6 Comments

Kidney failure

Image via youtube.com

Kidney failure is the Rodney Dangerfield of diseases, it really doesn’t get the respect it deserves. An estimated 660,000 Americans suffer from kidney failure and around 47,000 people die from it every year. That’s more than die from breast or prostate cancer. But now a new study has identified a promising stem cell candidate that could help in finding a way to help repair damaged kidneys.

Kidneys are the body’s waste disposal system, filtering our blood and cleaning out all the waste products. Our kidneys have a limited ability to help repair themselves but if someone suffers from chronic kidney disease then their kidneys are slowly overwhelmed and that leads to end stage renal disease. At that point the patient’s options are limited to dialysis or an organ transplant.

Survivors hold out hope

Italian researchers had identified some cells in the kidneys that showed a regenerative ability. These cells, which were characterized by the expression of a molecule called CD133, were able to survive injury and create different types of kidney cells.

Researchers at the University of Torino in Italy decided to take these findings further and explore precisely how CD133 worked and if they could take advantage of that and use it to help repair damaged kidneys.

In their findings, published in the journal Stem Cells Translational Medicine, the researchers began by working with a chemotherapy drug called cisplatin, which is used against a broad range of cancers but is also known to cause damage to kidneys in around one third of all patients. The team found that CD133 was an important factor in helping those damaged kidneys recover. They also found that CD133 prevents aging of kidney progenitor cells, the kind of cell needed to help create new cells to repair the kidneys in future.

Hope for further research

The finding opens up a number of possible lines of research, including exploring whether infusions of CD133 could help patients whose kidneys are no longer able to produce enough of the molecule to help repair damage.

In an interview in DD News, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine – praised the research:

“This is an interesting and novel finding. Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”

CIRM is funding several projects targeting kidney disease including four clinical trials for kidney failure. These are all late-stage kidney failure problems so if the CD133 research lives up to its promise it might be able to help people at an earlier stage of disease.

UC Irvine scientists engineer stem cells to “feel” cancer and destroy it

/ Todd Dubnicoff / 3 Comments

By blocking cell division, chemotherapy drugs take advantage of the fact that cancer cells multiply rapidly in the body. Though this treatment can extend and even save the lives of cancer patients, it’s somewhat like destroying an ant hill with an atomic bomb: there’s a lot of collateral damage. The treatment is infused through the blood so healthy cells that also divide frequently – like those in hair follicles, the intestines and bone marrow – succumb to the chemotherapy. To add insult to injury, cancers often become resistant to these drugs and metastasize, or invade, other parts of the body. Sadly, this spreading of a cancer is responsible for 90% of cancer deaths.

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UCI doctoral students Shirley Zhang, left, and Linan Liu are co-leading authors of the study. Photo: UC Irvine

Developing more specific, effective anti-cancer therapies is the focus of many research institutes and companies. While some new strategies target cell surface proteins that are unique to cancer cells, a UC Irvine (UCI) team has devised a stem cell-based technique that can seek out and destroy breast cancer cells that have metastasized in the lungs of mice by sensing the stiffness of the surrounding tissue. The CIRM-funded study was published this week in Science Translational Medicine.

While cells make up the tissues and organs of our bodies, they also secrete proteins and molecules that form a scaffold between cells called the extracellular matrix. This cell scaffolding is not just structural, it also plays a key role in regulating cell growth and other functions. And previous studies have shown that at sites of tumors, accumulation of collagen and other proteins in the matrix increases tissue stiffness and promotes metastasis.

Based on this knowledge, the UCI team aimed to create a cell system that would release chemotherapy drugs in response to increased stiffness. It turns out that mesenchymal stem cells – which give rise to bone, muscle, cartilage and fat – not only migrate to tumors in the body but also activate particular genes in response to the stiffness of their local cellular environment.  The researchers engineered mesenchymal stem cells to carry a gene that codes for a protein involved in the activation of a chemotherapy drug which is given by mouth. They also designed the gene to turn on only when it encounters stiff, cancerous tissue. They called the method a mechanoresponsive cell system (MRCS).

To test the MRCS, mice were infused with human breast cancer cells, which metastasized or spread to the lung. The MRCS-engineered mesenchymal stem cells were infused through the blood and homed to the lungs where they activated the chemotherapy drug which caused localized killing of the tumor cells with minimal damage to lung tissue. When the MRSC stem cells were given to mice without tumors, no increase in tissue damage was seen, proving that the MRSC-induced chemotherapy drug is only activated in the presence of cancerous tissue and has few side effects.

In a press release, team leader Weian Zhao, explained that these promising results could have wide application:

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Weian Zhao
Photo: UC Irvine

“This published work is focused on breast cancer metastases in the lungs. However, the technology will be applicable to other metastases as well, because many solid tumors have the hallmark of being stiffer than normal tissue. This is why our system is innovative and powerful, as we don’t have to spend the time to identify and develop a new genetic or protein marker for every kind of cancer.”

 

The team envisions even more applications. The MRCS could be engineered to carry genes that would enable detection with imaging technologies like PET scans. In this scenario, the MRCS could act as a highly sensitive detection system for finding areas of very early metastases when current techniques would miss them. They could also design the MRCS to activate genes that code for proteins that can break down and soften the stiff cancerous tissues which may inhibit the ability for a tumor to spread.

New target for defeating breast cancer stem cells uncovered

/ Todd Dubnicoff / 2 Comments

Stashed away in most of your tissues and organs lie small populations of adult stem cells. They help keep our bodies functioning properly by replenishing dying or damaged cells. Their ability to make more copies of themselves, as needed, ensures that there’s always an adequate supply set aside. But this very same self-renewing, life-sustaining property of adult stem cells is deadly in the hands of cancer stem cells. Also called tumor-initiating cells, cancer stem cells sustain tumor growth even after chemotherapy and are thought to be a primary cause of cancer relapse.

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Microscopic image of normal mouse mammary ducts. Mammary stem cells are found among basal cells (green). Image courtesy of Toni Celià-Terrassa and Yibin Kang, Princeton University

By studying adult and cancer stem cells side-by-side, Princeton researchers report this week in Nature Cell Biology that they’ve uncovered a common function in both cells types that not only helps explain an adult stem cell’s self-renewing ability but also points to new therapeutic approaches to targeting breast cancer stem cells.

Both adult and cancer stem cells continually resist signals from their environment that encourage them to specialize, or differentiate, into a particular cell type. Once specialized, the cells lose their ability to self-renew and will eventually die off. Now, if all the adult stem cells in an organ followed that instruction, they would eventually become depleted and the organ would lose the ability to repair itself. The same holds true for cancer stem cells which actually would be a good thing since it would lead to the tumor’s death.

The Princeton team first identified a molecule called miR-199a that allows mammary (breast) stem cells to resist differentiation signals by directly blocking the production of a protein called LCOR. Artificially boosting the amount of miR-199a led to a decrease in LCOR levels and an increase in stem cell function. But when LCOR levels were increased, mammary stem cell function was restricted.

The researchers then turned their attention to breast cancer stem cells and found the same miR-199a/LCOR function at work. In a similar fashion, boosting miR-199a levels enhanced cancer stem cell function and increased tumor formation while increasing LCOR restricted the tumor-forming ability of the breast cancer stem cells.

These lab results also matched up with tissue samples taken from breast cancer patients. High miR-199a levels in the samples correlated with low patient survival rates. But those with high levels of LCOR showed a better prognosis.

It turns out that cells in our immune system are responsible for boosting LCOR in mammary and breast cancer stem cells by releasing a protein called interferon alpha. So the presence of interferon alpha nudges mammary stem cells to mature into mammary gland cells and inhibits breast cancer stems from forming tumors. But in the presence of elevated miR-199a levels, mammary and breast cancer stem cells are protected and maintain their numbers by deactivating the interferon alpha/LCOR signal.

If you’re still with me, these results point to miR-199a as a promising target for restoring interferon-alpha’s cancer interfering properties. Team leader Dr. Yibin Kang highlighted this possibility in a Princeton University press release:

“Interferons have been widely used for the treatment of multiple cancer types. These treatments might become more effective if the interferon-resistant cancer stem cells can be rendered sensitive by targeting the miR-199a-LCOR pathway.”

Sleep inducing hormone puts breast cancer cells to rest  

/ Todd Dubnicoff / Leave a comment

It’s pretty easy to connect the dots between a lack of sleep and an increased risk of a deadly car crash. But what about an increased risk of cancer? A 2012 study of 101 women newly diagnosed with breast cancer found that those with inadequate sleep were more likely to have more aggressive tumors. Though the results of this survey were statistically significant, the biological connection between sleep and breast cancer is not well understood.

melatonin

Melatonin, the sleep hormone, may help fight cancer. Image Credit

Now, a report in Genes and Cancer by a Michigan State University research team shows that the interplay between melatonin, a hormone involved in sleep-wake cycles, and breast cancer stem cells may provide an explanation. And, more importantly, the study points to melatonin’s potential use as a cancer therapeutic.

Mammospheres: cancer in a more natural environment
To carry out their lab experiments, the researchers grew breast cancer cells into three-dimensional aggregates, called mammospheres, that resemble the tumor cell composition seen in an actual tumor in the body. This cell mix includes breast cancer stem cells which are thought to drive the uncontrolled tumor growth and reccurrence. David Arnosti, a MSU professor and co-author on the study, used a helpful analogy in a university press release to explain the importance of using the mammosphere technique:

“You can watch bears in the zoo, but you only understand bear behavior by seeing them in the wild. Similarly, understanding the expression of genes in their natural environment reveals how they interact in disease settings. That’s what is so special about this work.”

 

Melatonin fighting cancer cells via their stem cell-like properties
The cancer cells used in this study are also categorized as so-called estrogen receptor (ER) -positive cells. This classification means that the cancer growth is largely stimulated by the hormone estrogen.  The first round of experiments analyzed melatonin’s effects on estrogen’s ability to increase the growth and size of the mammospheres. The team also tested Bisphenol A (BPA), a chemical used in the plastics industry that mimics estrogen’s effects. While estrogen or BPA alone caused a large increase in mammosphere size and number, addition of melatonin stunted these effects.

Next, the team went deeper and looked at melatonin’s impact from a genes and proteins perspective. Estrogen is a steroid hormone that acts by passing through the cell wall and binding to the estrogen receptor inside the cell. Once bound by estrogen, the receptor travels to a cell’s nucleus and binds particular regions of DNA which can activate genes. One of those activated genes is responsible for producing OCT4, a protein that plays a critical role in a stem cell’s ability to indefinitely makes copies of itself and to maintain its unspecialized, stem cell state. This cellular pathway is how estrogen helps drives the growth of ER-positive breast cancer cells. The researchers showed that estrogen- and BPA-stimulated binding of the estrogen receptor to the OCT4 gene in the mammospheres was inhibited when melatonin was added to the cells.

Melatonin: putting cancer stems to bed?
Putting these observations together, melatonin appears to suppress breast tumor growth by directing inhibiting genes responsible for driving the stem cell-like properties of the breast cancer stem cells within the mammosphere. Melatonin is produced by the brain’s pineal gland which is only active at night. Once released, melatonin helps induce sleep. So a disrupted sleep pattern, like insomnia, would reduce melatonin levels and as a consequence the block on estrogen driven cancer growth is removed. ­

James Trosko, whose MSU lab perfected the mammosphere technique, sees these breast cancer results in a larger perspective:

“This work establishes the principal by which cancer stem cell growth may be regulated by natural hormones, and provides an important new technique to screen chemicals for cancer-promoting effects, as well as identify potential new drugs for use in the clinic.”

 

Keep in mind that these are very preliminary studies and more work is needed before a potential clinical application sees the light of day. In the meantime, have a good day and get a good night’s sleep.

 

 

Breast cancer: Piecing together early detection and treatment

/ Todd Dubnicoff / Leave a comment

Developing therapies for disease is kind of like trying to put together a series of incredibly complex puzzles. Scientists collect lots of “puzzle pieces”, in the form of data, through experiments in the lab and clinic or by reading up on other researchers’ results. Each piece gives researchers a tidbit of insight but the breakthroughs rely on connecting the pieces to see the whole picture.

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This is how the story has played out for a research team studying breast cancer at the Medical College of Georgia at Augusta University. Reporting last Friday in the American Journal of Pathology, the researchers connected the origin of several cell types present in breast tumor tissue to a common mutant precursor stem cell that is likely responsible for helping tumors thrive.

This finding was made possible by the identification of a mutation in the gene, GT198, that may not only provide a diagnostic tool for early breast cancer detection but also a totally new target for therapies. This is hopeful news for the one in eight women in the U.S. who will develop invasive breast cancer during their lifetime.

The GT198 gene carries the code for a protein that activates other genes in the presence of the hormone, estrogen. In its mutated form, GT198 protein no longer relies on estrogen to function and instead get stuck in the “on” position. Analyzing 249 human breast cancer tissues and 11 healthy samples, the researchers detected GT198 protein in breast tumor stromal tissue but not in the healthy samples.

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Anatomy of the breast. The cells of the stroma produce connective tissue and fat which support the lobules and ducts, structures that produce and deliver milk.

The stroma (meaning “mattress” in Greek) contains various cell types, some of which are responsible for producing fat and connective tissue, that provide structural support for the milk producing glands and ducts in the breast. But the presence of mutated GT198 in the tumor stromal tissue is thought to sabotage the cells into providing a favorable microenvironment for tumor growth. For instance, in one cell culture experiment, the team showed that mutant GT198 but not normal GT198 leads to increased angiogenesis, or new blood vessel growth, and fat production – activities associated with cancer initiation.

The presence of the mutant GT198 in not just one but several of the tumor stromal cell types, strongly suggests that they all come from the same stem cell or progenitor cell. Among the cells harboring the GT198 mutation, the pericytes – found in the stromal capillary blood vessels – also have significant amounts of CD44, a marker for progenitor cells, the progeny of stem cells. So the team hypothesizes that mutant pericytes are the precursor cells that give rise to the other mutant cells found in breast cancer stromal tissue.

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GT198 protein (brown staining) is specifically detected in various cell types found in breast cancer stroma. Tumor cells outside the stroma (panel K) don’t have GT198. Blue color indicates DNA.
Am J Pathol 2016, 186: 1-11

In an interview with MedicalResearch.com, senior author Kan Lo described the implications of these findings:

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Dr. Kan Lo

“In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendants so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer.”

 

One way of getting rid of those mutant progenitors could be by developing drugs that block the GT198 protein. Another exciting use of GT198 is as a diagnostic. Since the mutant stromal cells are important for providing the right conditions for tumor growth, it’s likely that they are present in the early stages of the cancer. So testing for the presence GT198 could be a tool for catching breast cancer early.

Sounds like we need to put together a few more puzzles before scientists can understand the full story of GT198 and breast cancer.

Stem cell stories that caught our eye: Parkinson’s trial revived, aspirin kills cancer stem cells and a stem cell role in mother-child obesity

/ Todd Dubnicoff / Leave a comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Parkinson’s clinical trials back on track.
After nearly 20 years of being stuck on the clinical trial “bookshelf”, an international team from Cambridge, UK revived a cell therapy for Parkinson’s disease.

In an announcement picked up this week by the Genetic Literacy Project, the team reported they had treated their first patient. Specifically, fetal brain cells were injected into the brain of a man in his mid-50’s with the disease.

Neurons derived from human embryonic stem cells

A fluorescent microscopic image of numerous dopaminergic neurons (the type of neurons that are degenerated in Parkinson’s disease patients) generated from human embryonic stem cells. Image courtesy of the Xianmin Zeng lab at the Buck Institute for Age Research.

In Parkinson’s, nerve cells controlling movement die for poorly understood reasons. An accumulation of data through the 60’s and 70’s suggested transplantation of fetal brain cells into the Parkinson’s brain would replace the lost nerve cells and restore movement control. After initial promising results in the 80’s and 90’s, larger clinical trials showed no significant benefit and even led to a worsening of symptoms in some patients.

Due to these outcomes, the research community shelved the approach. Insights gained in the interim pointed to more ideal brain injection sites in order to help avoid side effects. Also, follow up on patients beyond the two-year run of those early trials suggested that positive effects of the cell therapy may not emerge for at least three to five years. So this latest trial will run longer to capture this time window.

One remaining snag for this therapeutic strategy is the limited number of available cells for each transplant. So in the meantime, scientists including some of our grantees are working hard at getting embryonic stem cell- or iPS cell-based therapies to the clinic. Since stem cells divide indefinitely, this approach could provide an off-the-shelf, limitless supply of the nerve cells. Stay tuned.

Targeting cancer stem cells with the Wonder Drug.
Aspirin: it’s the wonder drug that may turn out to be even more wonderful.

Ball and stick model of aspirin, the wonder drug: relieves pain and prevents cancer

Ball and stick model of aspirin, the wonder drug: relieves pain and prevents cancer

Famous for relieving pain and preventing heart attacks, aspirin may add breast cancer-killer to its resume. This week a cancer research team at the Kansas City (Mo.) Veteran Affairs Medical Center published experiments picked up by Eureka Alert showing a daily dose of aspirin could put the brakes on breast cancer.

The analysis attributed this anti-cancer effect to aspirin’s capacity to reduce the growth of cancer stem cells. These cells make up a tiny portion of a tumor but if chemotherapy or radiation treatment leaves any behind, it’s thought the cells’ stem cell-like ability for unlimited growth drives cancer relapse and spread (metastasis).

In the study, mice with tumors given a daily low dose of aspirin for 15 days had, on average, tumors nearly 50% smaller than the aspirin-free mice. In another set of experiments, the team showed aspirin could prevent tumors as well. Mice were given aspirin for 10 days before exposing them to cancer cells. After another 15 days, the aspirin treated animals had significantly less tumor growth compared to an untreated group.

Senior author Sushanta Banerjee stands behind these findings: he’s been taking an aspirin a day for three years but stresses that you should consult with your doctor before trying it yourself.

A stem cell link to the passing on of obesity from mom to child?
It’s been observed that children of obese moms have a high risk for obesity and diabetes. You might conclude that genetics are the culprit as well as lifestyle habits passed down from parent to child. But research published this week by researchers at the University of Colorado School of Medicine suggests another mechanism: they conclude the mere presence of the growing embryo in the uterus of an obese mother may instruct the child’s cells to take on more fat.

The team’s reasoning is based on an analysis of umbilical cord blood stem cells collected from babies born to 12 obese mothers and 12 normal weight mothers. In the lab, the stem cells were specialized into fat and muscle cells. The cells from babies of obese mothers showed increased fat accumulation and a lower production of proteins important for uptake of blood sugar (a state that could eventually tip the scales towards diabetes).

Certainly it’s a leap to link the property of cells in a dish to the eventual health of a child. But the results are intriguing enough that the researchers intend to follow the children as they get older to look for more connections between the state of the kids’ stem cells and their health profile.