Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

cancer

Heated, targeted chemotherapy helps abdominal cancers

Cancer of the colon, ovaries, appendix or other organs within the abdomen often spreads to the lining of the abdominal cavity. Experts call this condition peritoneal surface malignancy. Until recently, treatment options for this form of cancer only provided relief from symptoms.

Emory University Hospital is one of a few facilities nationwide to utilize a new combination therapy to slow or prevent recurrence of this cancer. Hyperthermic intraperitoneal chemoperfusion (HIPEC) is a procedure done immediately following surgery that delivers heated chemotherapy directly into the abdominal cavity where it can penetrate cancerous tissue. Heat at 42 C (107 F) destroys cancer cells and enhances the power of chemotherapy.

The term “intraperitoneal” means that the treatment is delivered to the abdominal cavity. “Hyperthermic chemoperfusion” means that the solution containing chemotherapy is heated to a temperature greater than normal body temperature.

Charles Staley, MD, chief of surgical oncology at the Emory Winship Cancer Institute, says by bathing the abdomen with heated chemotherapy immediately following surgery doctors can administer a higher dose of medication than would normally be tolerated by a patient if given intravenously – the traditional way chemotherapy is administered.

During surgery, Staley removes all visible tumors throughout the abdomen, a procedure known as cytoreductive surgery. Following surgery, while still in the operating room, Staley administers the new treatment, which takes about two hours. Recent studies show improved prognosis in patients treated with HIPEC after the cytoreductive surgery.

Illustration of heated chemo therapy

Illustration of heated, targeted chemotherapy

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Strategies to target cancer stem cells

A story in last Friday’s New York Times highlights research on “cancer stem cells”: a fraction of cells in a tumor that are especially resistant to chemotherapy and resemble the body’s non-cancerous stem cells in their ability to renew themselves.

The story describes work by a team at the Broad Institute, who reported in the journal Cell that they had identified compounds that specifically kill cancer stem cells. The hope is that compounds such as these could be combined with conventional treatments to more effectively eliminate cancers.

However, scientists disagree on whether the phenomenon of cancer stem cells extends to different kinds of cancer and what is the best way to target them. Previously not much was known about how to attack these cells.

Work at Emory’s Winship Cancer Institute has been tracking how some biomarkers in cancer cells resemble or differ from those found in stem cells. These markers may help researchers home in on the cancer stem cells.

 

Anticancer therapy must target more than one type of cell. TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor

If "cancer stem cells" play the critical roles some scientists think they do, anticancer therapy must target more than one type of cell. In this figure from Van Meir + Hadjipanayis' review, TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor cells.Â

 

 

In a recent review, Emory brain cancer specialists Erwin Van Meir and Costas Hadjipanayis write:

The “cancer stem cell” hypothesis has invigorated the neuro-oncology field with a breath of fresh thinking that may end up shaking the foundation of old dogmas, such as the widely held belief that glioblastoma tumors are incurable because of infiltrative disease. If the infiltrated cells are in fact differentiated tumor cells, their dissemination beyond the surgical boundary may not be the primary cause of tumor recurrence.

Van Meir, the editor of a new book on brain cancer, adds this comment:

Clearly a lot more work needs to be done to understand the precise cause of glioblastoma recurrence after surgery and chemotherapy and how to prevent it.  The possibility of developing therapeutics that can specifically target the brain cancer stem cells is an exciting new development but will have to proceed with caution to spare normal stem cells in the brain. Developing new imaging tools that can track cancer stem cells in the brain of treated patients is also an important objective and some of the Emory investigators are evaluating the use of nanoparticles to this purpose.

A new faculty member at Winship, Tracy-Ann Read, recently published her research on a molecule that could be used to identify “tumor-propagating cells” in medulloblastoma, a form of brain cancer. She says:

Although cancer stem cells have been identified in many different types of cancer, it is becoming increasingly clear that the properties of these cells may vary greatly among the different tumor types. It is unlikely that one  therapeutic agent will be able to target the cancer stem cells in for example all types brain tumors. Hence  much work still needs to be done in terms of analyzing the properties of these cells in each tumor type and identifying the genes that are responsible for their unique ability to propagate the tumors. 

Winship’s director Brian Leyland-Jones has also reported at the San Antonio Breast Cancer Symposium that molecules that distinguish a hard-to-treat form of breast cancer resemble those that maintain stem cells.

Nice round-up from Nature’s stem cell blog editor Monya Baker

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Childhood cancer treatment may raise diabetes risk

Cancer survivors who got radiation treatments as children have nearly twice the risk of developing diabetes as adults. That’s according to a study led by Emory and Children’s Healthcare of Atlanta pediatric oncologist Lillian R. Meacham, MD.

Lillian Meacham, MD

Lillian Meacham, MD

The study, published in the August 10/24 issue of Archives of Internal Medicine, compared rates of diabetes in nearly 8,600 childhood cancer survivors diagnosed between 1970 and 1986, and nearly 3,000 of their siblings who did not have cancer.

Children who were treated with total body radiation or abdominal radiation to fight off cancer appear to have higher diabetes risks later in life, regardless of whether they exercise regularly or maintain a normal weight.

After adjusting for other risk factors, including body mass index – a ratio of height and weight – Meacham and team found that childhood cancer survivors overall were 1.8 times more likely to have diabetes.

And the more radiation that was used, the greater the diabetes risk. For those treated with total body radiation — a treatment often used before bone marrow transplants to treat childhood leukemia — the diabetes risk was more than seven times greater.

More study is needed to understand how radiation could promote diabetes in cancer survivors, notes Meacham.

She says it is imperative that clinicians recognize this risk, screen for diabetes and pre-diabetes when appropriate, and approach survivors with aggressive risk-reducing strategies.

Meacham is a professor of pediatrics in the Emory School of Medicine and medical director of the Cancer Survivor Program with the AFLAC Cancer Center and Blood Disorders Services, Children’s Healthcare of Atlanta.

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Aspirin may aid colorectal cancer survival

This week’s Journal of the American Medical Association (JAMA) reports on the potential benefits of aspirin following a colorectal cancer diagnosis.

Dr. Vincent Yang

Vincent Yang, MD, PhD

Emory digestive disease expert Vincent W. Yang, MD, PhD, professor and director of the Division of Digestive Diseases, Emory School of Medicine, comments on the new study:

A large body of evidence shows that regular aspirin use can reduce the formation of colorectal cancer. Aspirin inhibits the activity of an enzyme called cyclooxygenase-2, or COX-2, that is often over-expressed in colorectal cancer.

In the Aug. 12 issue of JAMA, a study led by Andrew Chan, MD, MPH, of the Harvard Medical School, shows that regular aspirin use reduces deaths in patients who had been diagnosed with colon cancer. The study includes two large, diverse groups of individuals who were followed for more than 20 years for various health-related issues.

The individuals who developed colorectal cancer during the follow–up period and had used aspirin regularly had a lower death rate than those patients who developed colon cancers and did not take aspirin. More importantly, the benefit patients received from regularly using aspirin was more apparent if their cancers were positive for COX-2.

The results of this new study are consistent with the earlier finding reported in medical journals about aspirin’s chemopreventive effect on colorectal cancer. However, it should be noted that this study is observational by nature and that regular aspirin use can result in significant toxicities.

To learn more about the routine use of aspirin as an adjunct treatment for colorectal cancer, studies that are blinded and randomized placebo-controlled are necessary. Such clinical trials have been conducted which proved that aspirin taken at 81 mg or 325 mg per day is effective in preventing the recurrence of colorectal adenomas (polyps) after they are removed during screening colonoscopy.

A similar clinical trial could be conducted to test the ability of aspirin to prevent colorectal cancer recurrence. Perhaps patients could first be classified based on the COX-2 levels in their tumors before being randomized into the trial. A potential outcome would be that patients with COX-2-positive tumors would receive more benefit from aspirin use than those with tumors that are COX-2-negative. Chan’s JAMA findings are a catalyst for further study.

Yang is also professor of hematology and oncology at Emory Winship Cancer Institute.

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Rapid radiation delivery increases accuracy

RapidArc for prostate cancer

RapidArc for prostate cancer

Doctors in Emory’s Department of Radiation Oncology are the first in Georgia to use a new radiation delivery system that speeds up treatment and increases accuracy.

The first patients treated have been men with prostate cancer, but the treatment can also be used for patients with head and neck cancers or brain tumors, says Walter Curran, MD, chair of the department and chief medical officer of the Emory Winship Cancer Institute.

Curran says the main advantage to the new system, called RapidArc, is faster treatment so a patient is not lying on a treatment table for a long period of time. Limiting the time it takes can help with patient comfort as well as minimizing the chance of movement, which affects accuracy during treatment.

Treatments that once took five to 10 minutes can be performed in less than two minutes. For patients getting radiation daily over several weeks, that can make a significant difference, Curran says.

Emory University Hospital and Emory University Hospital Midtown both have the RapidArc system. Emory Health magazine features RaapidArc this month.

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Cancer survivors may have psychological distress

Long-term survivors of cancer that developed in adulthood are at increased risk of experiencing serious psychological distress, according to a report in the July 27 issue of Archives of Internal Medicine.

The estimated 12 million cancer survivors in the United States represent approximately 4 percent of the population.

Commenting on this week’s study, Michael Burke, MD, clinical director of psychiatric oncology at Emory Winship Cancer Institute, says only recently has the emotional wellbeing of cancer patients been given serious consideration by physicians and patients. Yet, easing the disease’s emotional burden on patients and families may improve patients’ treatment and prognosis.

Michael Burke, MD

Michael Burke, MD

Burke has conducted studies focused on the effects of the disease’s emotional burden on patients and families and whether easing that burden can improve patients’ treatment and coping skills. Burke and his colleagues offer a collaborative approach toward therapies for the emotional, psychological, and physical symptoms associated with cancer and its treatment.

A history of cancer may affect current mental health in several ways, says the Archives study author and Brigham and Women’s Hospital and Dana-Farber Cancer Institute researcher. The researcher reports that cancer diagnosis and treatment can produce delayed detrimental effects on physical health and functioning such as secondary cancers, cardiac dysfunction, lung dysfunction, infertility, neurological complications and neurocognitive dysfunction. A cancer history, they continue, can also affect social adaptation, employment opportunities and insurance coverage. Adjusting to these functional and life limitations may create long-term psychological stress.

Emory’s Burke says to help patients cope with a diagnosis of cancer, he and his colleagues evaluate patients’ medical and personal history, environment and health behaviors, such as whether they’re getting enough exercise or increasingly using alcohol and tobacco.

Listen to Burke’s own words on Sound Science about how he helps patients cope with the emotional aspects of cancer.

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