Stem Cell Clinic

Breast cancer: Changes in immune cell composition linked to future risk – Medical News Today

For the first time, researchers have quantified the composition of various types of immune cell in breast tissue and assessed whether it is linked to later risk of breast cancer.

In the journal Clinical Cancer Research, the team - from the Mayo Clinic in Rochester, MN - suggests that the findings reveal important clues about the role of the immune system in the early stages of breast cancer development.

First author Dr. Amy Degnim is a breast surgeon who specializes in the study of breast tissue for very early signs of premalignant change.

She says the new study supports the idea that immune-related approaches such as vaccines may be effective in preventing breast cancer.

Breast cancer is cancer that begins in the cells of the breast, although it can spread to other parts of the body. It can occur in both men and women, but it is rare in men.

In the United States, breast cancer is the second most common cancer in women after skin cancer.

Based on current incidence rates, a woman born in the U.S. today has a 1 in 8 chance of developing breast cancer during her lifetime.

For their case-controlled study, Dr. Degnim and colleagues quantified various types of immune cell in different types of breast tissue. They used samples of normal breast tissue from donors to the Susan G. Komen for the Cure Tissue Bank, and samples of breast tissue from women diagnosed with benign breast disease at the Mayo Clinic.

Fast facts about breast cancer

Learn more about breast cancer

Benign breast diseases are noncancerous breast conditions such as cysts and fibrosis that present as lumps and thickening of tissue in the breast.

Some noncancerous breast conditions may not present symptoms and may only be found during a mammogram. Sometimes, however, they can present in a similar way to breast cancer, so it can be hard to differentiate them from breast cancer just from symptoms alone.

Unlike breast cancers, benign breast diseases are not life-threatening, but some are connected with a higher risk of developing breast cancer later in life.

Some of the study participants with benign breast disease went on to develop breast cancer later.

Altogether, the researchers collected data on 94 age-matched triplets.

Each triplet comprised: a normal breast tissue case; a benign breast disease case in which the donor developed breast cancer later; and a benign breast disease case where the donor remained cancer-free.

The results showed that the composition of immune cells in the breast tissue was different in the three different types of donor.

For example, compared with normal breast tissue, breast tissue from donors with benign breast disease had higher proportions of certain immune cells, particularly dendritic cells and macrophages. These types of immune cell work together to create an immune response.

The researchers also found that tissue from donors with benign breast disease who later developed breast cancer showed lower levels of B cells - a type of immune cell that produces antibodies.

They suggest that the reduced levels of B cells in breast tissue of women with benign breast disease who later develop cancer indicates that B cells may play an important role in preventing disease progression, and they may serve as a biomarker for breast cancer risk.

"Our findings provide evidence that the immune system may have an important role in promoting or inhibiting breast cancer development in its very earliest stages."

Dr. Amy Degnim

Learn how the spread of triple-negative breast cancer could be halted with existing drug.

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Breast cancer: Changes in immune cell composition linked to future risk - Medical News Today

Educational seminar on stem cell therapy to be featured at lunch meeting in Abilene – Salina Post

Kansas Regenerative Medicine Center (KRMC) staff will be the guest speakers at the next Healthwise 55 luncheon. Speakers Frank Lyons, MD; John Farley (Founder); and Kate Farley will define stem cells and explain their many therapeutic uses. The KRMC staff will also share how stem cell therapy is a potential alternative to joint replacements or other medical therapies.

The event will be on Thursday, February 23, from noon to 1 p.m. in the Conklin Conference Center at Memorial Hospital, located at 511 N.E. 10th, Abilene. The cost is $5.00 to cover the price of the meal. Please call Michelle McClanahan, MHS Director of Volunteer Services, at (785) 263-6692 by Monday, February 20, to make a reservation.

Healthwise 55 is a luncheon and health information program hosted by the MHS Volunteer Corps. It is open to the public for individuals ages 55 and older. It includes a meal followed by a health care professional(s) speaking on a health-related topic.

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Educational seminar on stem cell therapy to be featured at lunch meeting in Abilene - Salina Post

Vital links between brain tumors and epileptic seizures – Science Daily

Detecting brain tumors at the earliest possible stage and eliminating them before seizures begin might be possible one day, according to research by scientists at Baylor College of Medicine and Texas Children's Hospital.

In the study, which is published in the journal Nature Neuroscience, the scientists report that the emergence of specific brain cells during brain tumor progression in a mouse model marked the onset of seizures and brain tumor invasion. An improved understanding of how brain tumors cause seizures can potentially lead to strategies to prevent them or treat them.

"We began this project by studying normal brain cells," said co-senior author Dr. Benjamin Deneen, associate professor in the Center for Stem Cell and Regenerative Medicine at Baylor and the Neurological Research Institute at Texas Children's Hospital. "The brain has billions of cells of which only 30 percent are neurons. Astrocytes are the predominant cell type of the remaining 70 percent. Surprisingly, astrocytes have not been studied in as much detail as neurons have."

"Although astrocytes are often broadly categorized as one cell type, a lot of diversity exists in the functions carried out by these cells," said co-senior author Dr. Chad Creighton, associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor.

Astrocytes play diverse roles in the brain, from supporting the functions of neurons, participating in synapse formation and function and in the release of neurotransmitters, to making the blood-brain barrier and other functions. What is not known is whether all these functions are carried out by different subpopulations of astrocytes. This study explores the cellular and functional diversity of the most enigmatic, yet most abundant cell type in the brain. Answering this fundamental question served as the starting point for this investigation.

Better understanding the underappreciated astrocyte

The researchers took populations of mouse astrocytes, which until now have been considered to be a cell type with little diversity, and used molecular markers expressed on the cells' surface to divide the cells into subpopulations according to the cell surface markers expressed. They identified five subpopulations -- the scientists called them subpopulations A, B, C, D and E -- each containing a unique combination of cell surface markers. These subpopulations were consistently present across several different regions of the brain.

Further studies showed that each subpopulation of astrocytes expressed distinct sets of genes. These molecular signatures suggested that each subpopulation might play different roles in the brain. In particular, the scientists were interested in subpopulation C, which expressed a significant number of genes associated with synapses, the junctions that transmit nerve impulses that connect networks of neurons in the brain.

The researchers compared the ability of the different subpopulations of astrocytes to support the formation and function of synapses between neurons.

"In the laboratory, we combined individual subpopulation of astrocytes with neurons and measured synapse formation and function," said Deneen. "We found that neurons incubated with subpopulation C made more synapses than neurons incubated with the other subpopulations."

Taken together, these results revealed that astrocytes in the normal mouse brain comprise at least five distinct subpopulations that differentially support synapse formation and function.

Linking astrocytes to human glioma

"Astrocytes are associated with numerous neurological conditions, including injury, multiple sclerosis, autism, schizophrenia, Alzheimer's and Parkinson's disease and brain tumors. Given that we found diverse astrocyte subpopulations, we wondered whether these subpopulations could also explain astrocyte contributions to a host of different neurological diseases," Deneen said.

One of the interests of the Deneen lab is identifying mechanisms that regulate astrocyte development and how these cells contribute to neurological diseases, in particular human glioblastoma multiforme, the most aggressive and deadly type of brain tumor. In these type of cancer, about 80 percent of the tumor comprises transformed astrocyte-like cells, and, just as in the case of normal brain tissue, the diversity of these tumor cell subpopulations and functions in brain tumors had not been studied in detail.

In this case, the scientists used a different approach to determine whether astrocyte-like cells in human glioblastoma include different astrocyte subpopulations.

"We used publicly available genomic datasets to help us understand what distinguishes the different types of astrocytes from each other," Creighton said. "The genomic datasets compile entire genomes -- all the genes -- of different types of cells. Using this resource, we discovered that each type of human astrocyte showed very distinctive patterns of gene activation. It was by comparing these patterns with patterns associated with brain cancer or with epilepsy, using public data, that we discovered how specific types of astrocytes appear to have roles in these diseases."

To support that astrocytes seemed to play a role in human glioblastoma, the researchers genetically engineered two mouse models of the disease and observed that the astrocyte subpopulations are also present in mouse tumors. The subpopulations are also present in primary human specimens of human glioblastoma multiforme.

Astrocytes and seizures

One striking characteristic of glioblastoma, which usually leads to the discovery of the tumor, is epileptic seizures.

On one occasion Deneen was talking with Dr. Jeffrey L. Noebels, about this research. Noebels, who is professor of neurology, neuroscience, and molecular and human genetics, director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor and is a leader in the field of epilepsy, asked Deneen, "do your mice with brain tumors have seizures?" "They do," Deneen said.

This conversation led to planning a series of experiments in the mouse models of glioma to determine the time scale of the seizures and whether different sub populations of astrocyte-like cells within the tumor were associated with seizures.

The results of these experiments showed that as the tumor grows, the excitability of the adjacent neurons progressively increases. Seventy days after birth, the mice had visible seizures that correlated with the emergence of astrocyte subpopulation C. Further linking these astrocyte-like subpopulations to seizures, the scientists showed that subpopulation C expresses a significant number of genes linked to epilepsy.

While subpopulation C seems to be involved with seizures in the mouse model of glioblastoma, subpopulations B and D showed they were able to migrate more in laboratory assays than population C.

"Taken all together, the evidence from the mouse model of glioblastoma indicates that as the tumor evolves, different subpopulations of astrocyte-like cells develop within the tumor and execute distinct functions that are related to two important tumor characteristics, synaptic imbalance that can lead to seizures, and tumor migration that can lead to tumor invasion of other tissues," Deneen said.

"Less than half of the patients with epilepsy caused by a brain tumor can be helped with existing antiepileptic drugs," said Noebels, co-author of the work. "We do not understand exactly how malignant cells cause seizures, or why seizures persist after tumor surgery. Until now, we could only study this brain tissue at later misleading stages. I am excited that this next-generation experimental model in mice will allows us to study, for the first time, the earliest effects of human tumors on brain circuits before seizures actually begin and understand the mechanisms. These studies would be a major advance in patient care, allowing clinicians to bypass precious months spent searching for effective therapy to stop seizures. Because seizures themselves damage brain tissue, timely effective therapy is of the essence."

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Vital links between brain tumors and epileptic seizures - Science Daily