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

Nanotechnology may help surgeons detect cancer

What a cancer patient wants to know after surgery can be expressed succinctly: “Did you get everything?” Having a confident answer to that question can be difficult, because when they originate or metastasize, tumors are microscopic.

Considerable advances have been made in “targeted therapy” for cancer, but the wealth of information available on the molecular characteristics of cancer cells hasn’t given doctors good tools for detecting cancer during surgery – yet.

Even the much-heralded advent of robotic surgery has not led to clear benefits for prostate cancer patients in the area of long-term cancer control, a recent New York Times article reports.

At Emory and Georgia Tech’s joint department for biomedical engineering, Shuming Nie and his colleagues are developing tools that could help surgeons define tumor margins in human patients.

Read more

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Lung cancer clinical trial shows treatment promise

Advanced non-small cell lung cancer (NSCLC) is a challenging disease to treat. More than 200,000 new cases of lung cancer are diagnosed each year, and 85 percent to 90 percent of diagnosed lung cancers fall into the non-small cell type.

A new strategy for treating NSCLC that increases the effectiveness of standard chemotherapy in patients with advanced stage disease has been found by Emory researchers. Recent advances in treatment result in improvement in patient survival noted for all stages of NSCLC.

Saresh Ramalingam, MD

Saresh Ramalingam, MD

Lead investigator Suresh Ramalingam, MD, associate professor of hematology and medical oncology at Winship Cancer Institute of Emory University, along with a consortium of academic institutions that is supported by the National Cancer Institute, published the positive results in The Journal of Clinical Oncology.

In the clinical trial, Emory scientists added a cancer-fighting compound that is used to treat a specific type of lymphoma to standard lung cancer chemotherapy, resulting in an increase in positive response rates in NSCLC patients.

The addition of vorinostat, a compound that affects the function and activity of DNA and various other proteins, to standard chemotherapy treatment of carboplatin and paclitaxel, increased positive response rates in patients from 12.5 percent to 34 percent in a clinical trial of 94 patients with metastatic non-small cell lung cancer.

Vorinostat may be affecting histones, which are spool-like proteins around which the cell’s DNA is wound. These proteins are important for cell division. We believe these molecular effects could enhance the efficacy of carboplatin and paclitaxel, respectively.

Vorinostat is part of an emerging class of anti-tumor agents that interfere with enzymes known as histone deacetylases (HDAC). Inhibiting these enzymes increases the level of acetylation, a modification of proteins in the cell. Vorinostat is sold by Merck as Zolinza and was approved by the FDA in 2006 to treat cutaneous T cell lymphoma.

Ramalingam says this exciting data will have to be further evaluated in confirmatory phase III studies before they can be adopted in routine use. However, HDAC inhibitors can now be considered among the leading targeted agents under evaluation for the treatment of non-small cell lung cancer.

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Questions only a network of pathologists can answer

When a patient is fighting a brain tumor, pathologists usually obtain a tiny bit of the tumor, either through a biopsy or after surgery, and prepare a microscope slide. Looking at the slide, they can sometimes (but not always) tell what type of tumor it is. That allows them to have an answer, however tentative, for that critical question from the patient: “How long have do I have?” as well as give guidance on what kind of treatment will be best.

Dan Brat, a pathologist specializing in brain tumors at Emory Winship Cancer Institute, gave a presentation this week explaining how he has been asking more complicated questions, ones only a network of pathologists armed with sophisticated computers can answer:

  • What genes tend to be turned on or off in the various types of brain tumors?
  • What does the pattern look like when a tumor is running out of oxygen?
  • What if we get a “robot pathologist” to look at hundreds of thousands of brain tumor slides?
Under the microscope, the shapes of cell nuclei in brain tumors look different depending on the type of tumor.

Under the microscope, the shapes of cell nuclei in brain tumors look different depending on the type of tumor.

Brat was speaking at a caBIG (cancer Biomedical Informatics Grid) conference, taking place at the Emory Conference Center this week. caBIG is a computer network sponsored by the National Cancer Institute that allows doctors to share experimental data on cancers. Brat explained that low-grade brain tumors come in two varieties: oligodendrogliomas and astrocytomas. Under the microscope, cell nuclei in the first tend to look round and smooth, but the second look elongated and rough. Kind of like the differences between an orange and a potato, he said.  He and colleague Jun Kong designed a computer program that could tell one from the other. They had the program look through almost 400,000 slides, using resources compiled through caBIG (Rembrandt and Cancer Genome Atlas databases). Sifting through the data, they could find that certain genes are turned on in each kind of tumor.

Imagine a "robot pathologist" that can sift through thousands of images from brain tumor samples.

Imagine a "robot pathologist" that can sift through thousands of images from brain tumor samples.

Daniel Brat, MD, PhD, principal investigator for the In Silico Brain Tumor Research Center

Daniel Brat, MD, PhD, principal investigator for the In Silico Brain Tumor Research Center

Eventually, this kind of information could help a patient with a brain tumor get good responses to those “How long?” and “How am I going to get through this?” questions.

Joel Saltz, who leads Emory’s Center for Comprehensive Informatics, has been a central figure in developing tools for centers such as Emory’s In Silico Brain Tumor Research Center. In September 2009, Emory was selected to host one of five “In Silico Research Centers of Excellence” by the National Cancer Institute.

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Mammography can save lives by following ACS guidelines

The recent recommendation issued by the U.S. Preventive Services Task Force to revise screening mammography guidelines has generated considerable confusion and worry among women and their loved ones, says Carl D’Orsi, MD, FACR, director of the Emory Breast Imaging Center.

Carl D'Orsi, MD

Carl D'Orsi, MD

D’Orsi says he is counseling women who are concerned about mammograms and deciding what screening schedule to follow that they should use the long-established American Cancer Society guidelines: annual screening using mammography and clinical breast examination for all women beginning at age 40.

The recent recommendations by the task force advise against regular mammography screening for women between ages 40 and 49. It suggests that mammograms should be provided every other year (rather than yearly) for women between ages 50 and 74, and then breast cancer screening in women over 74 should be discontinued.

Mammography is not a perfect test, but it has unquestionably been shown to save lives, says D’Orsi, professor of radiology and of hematology and oncology in the Emory’s School of Medicine, and program director for oncologic imaging at Winship Cancer Institute of Emory. Since the onset of regular mammography screening in 1990, the mortality rate from breast cancer, which had been unchanged for the preceding 50 years, has decreased by 30 percent.

Winship Cancer Institute of Emory University

Winship Cancer Institute of Emory University

These new recommendations – which are based on a review that did not include experts in breast cancer detection and diagnosis – ignore valid scientific data and place a great many women at risk, continues D’Orsi.

Ignoring direct scientific evidence from large clinical trials, notes D’Orsi, the task force based its recommendations to reduce breast cancer screening on conflicting computer models and the unsupported and discredited idea that the parameters of mammography screening change abruptly at age 50.

The task force commissioned their own modeling study and made recommendations in reliance on this study before the study had ever been published, made public or held to critical peer review, and did not use both randomized, controlled trials and already-existing modeling studies, explains D’Orsi.

If Medicare and private insurers adopt these flawed recommendations as a rationale for refusing women coverage of these life-saving exams, it could have deadly effects for American women, says D’Orsi.

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Reducing stress in cancer patients and caregivers

Emory’s Susan Bauer-Wu, PhD, RN, is recognized both nationally and internationally for her understanding of the mind-body connection and enhancing the quality of life for individuals affected by cancer. Her research programs aim to make a difference in the care that cancer patients receive and in the health of family caregivers. She is a national leader in palliative care and integrative medicine and health.

Susan Bauer-Wu, PhD, RN

Susan Bauer-Wu, PhD, RN

Bauer-Wu, nurse scientist and Georgia Cancer Coalition Distinguished Cancer Scholar, joined Emory’s Nell Hodgson Woodruff School of Nursing and Emory Winship Cancer Institute faculties in 2007.

Bauer-Wu studies whether psycho-behavioral interventions have a positive effect on psychological and physical health. She is currently conducting a large randomized clinical trial that looks at whether meditation affects subjective symptoms as well as lab findings such as stress hormones or how long a patient’s white blood cells take to recover after a bone marrow transplant.

This National Institutes of Health (NIH)-funded study has enrolled 241 patients at Emory and the Dana-Farber Cancer Institute, where Bauer-Wu previously served as director of the Phyllis F. Cantor Center for Research in Nursing and Patient Care Services. The study will finish in 2010. Bauer-Wu is also involved in research with neuro-imaging to see what parts of the brain respond to such interventions.

Bauer-Wu says mindfulness meditation provides skills for the cancer patient to better cope with stressful circumstances, and in turn, the stress response can be minimized, and a sense of well-being ensues, and the cancer patient feels more relaxed, in control and physically comfortable. Bauer-Wu’s interest in cancer patients began early in her career when she worked as an oncology nurse.

In addition, she recently received a $3.5 million NIH grant for a study aimed at reducing heart disease risk and improving health and wellbeing among family caregivers of dementia and heart failure patients.

Recently, the American Academy of Nursing inducted Bauer-Wu into its new Fellowship class of 98 top national nursing. Fellows are elected through a highly selective process that recognizes individuals who have made major contributions to nursing and health care and whose work has influenced health policies benefiting all Americans.

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Expandable implants utilize magnets for treatment

One of the most exciting areas in the treatment of pediatric extremity sarcomas is the development of expandable implants and a procedure that uses magnets to treat sarcoma of bone and soft tissue.

The latest devices allow lengthening of the bone using a non-invasive technique with a simple magnet held against the patient’s leg, which preserves the patient’s own joint. These implants can be expanded and grow with the patient as they get taller without multiple operations.

The patient’s leg is put through a round magnet every few months and, using different settings, the physician can turn the magnet on and patients can watch their leg get longer. There are only a few centers in the country performing this procedure – Emory Musculoskeletal Oncology and Limb Reconstruction Center is the only center in Georgia that offers this treatment.

David K. Monson, MD, Emory assistant professor of orthopaedic surgery, and Shervin V. Oskouei, MD, Emory assistant professor of orthopaedic surgery, lead the Emory Musculoskeletal Oncology and Limb Reconstruction Center.

Monson’s focus is on rare tumors, sarcomas of the bone and soft tissue as well as other uncommon benign bone and soft tissue tumors. He also treats metastatic cancers that have spread to areas of the bone from other primary malignancies, and often performs complex reconstructive procedures for these disorders not available in the community. Oskouei is an expert in the treatment of musculoskeletal (extremity) tumors, total hip and total knee replacements and revisions. His specialty is in orthopaedic oncology.

Monson and Oskouei point to the advantages of the procedure:

  • The procedure can save the patient’s limb by avoiding amputation.
  • The procedure can be done in one operation so patients don’t have to make multiple trips to the operating room, using one implant that can be expanded as the patient grows.
  • It allows lengthening of the bones and maintains an equality in limb length.
  • The technique is noninvasive and can be done in the office using just a mild anesthetic, rather than general anesthesia.
  • The procedure can be done more frequently, allowing physicians to lengthen in much smaller increments, which is much safer and more comfortable for the patient.
  • The procedure provides patients improved function — patients are able to put their full weight on their leg immediately after surgery

Learn more from patient Ned Crystal or visit Emory Healthcare.

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Serendipity & strategy: Nox researcher David Lambeth

David Lambeth, MD, PhD, with one of his paintings

David Lambeth, MD, PhD, with one of his paintings

NADPH oxidases (Nox for short) are enzymes that help plants fight off pathogens, guide sexual development in fungi, are essential for egg laying in flies and even help humans to sense gravity.

But what first attracted the interest of Emory researchers was the role of Nox in vascular disease and cancer. Along with Emory cardiologist Kathy Griendling, pathologist David Lambeth pioneered the discovery of how important these reactive oxygen-generating enzymes really are.

Lambeth will be honored this month in San Francisco by the Society for Free Radical Biology and Medicine with their 2009 Discovery Award. A profile in Emory Report explores his musical and artistic pursuits as well as his science.

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Look, don’t touch – noninvasive biochemistry

Much of the time in biochemistry, when you want to know what’s happening inside a cell you have to break them open.

Fluorescent proteins are a great tool and deserved their Nobel Prize. But you have to convince your favorite cells to make the fluorescent proteins first. It’s possible to think of specialized non-invasive probes too: dyes that change color when they encounter calcium, for example.

Now imagine being able to decipher what’s going on inside cells simply by looking at them and watching the proteins and organelles shift in response to signals. That’s essentially what Yuhong Du and Haian Fu at the Emory Chemical Biology Discovery Center have been able to do.

They use an “optical biosensor” which puts cells in front of a reflective grating. Depending on how the grating reflects light, they can measure mass redistribution inside the cells.

How the optical biosensor works

How the optical biosensor works

With this technology, they could watch for responses as cancer cells responded to signals from EGFR (epidermal growth factor receptor).

Drugs such as gefitinib and erlotinib are supposed to block those growth signals in lung cancer cells, but not every cancer responds to them. These results suggest that the optical biosensor system could be used to screen for compounds that block EGFR and many other receptors, potentially speeding up the hunt for drugs against several diseases.

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Obesity ups risk for endometrial cancer

Increasing numbers of obesity in both men and women nationwide are resulting in a growing rate of multiple health consequences. Recent research suggests that overweight women are at an increased risk of developing endometrial cancer, especially if menopause occurs in women younger than age 45.

One study has found that women with a body mass index (BMI) of greater than 35, who experienced their last menstrual period at an age younger than 45, had more than 20 times the risk of developing endometrial cancer than normal-weight women.

BMI is a measure of body fat based on height and weight that applies to both adult men and women. A BMI of 18.5 to 24.9 is considered normal weight, 25 to 29.9 is considered overweight and a number over 30 is considered obese.

Mary Dolan, MD, MPH, assistant professor of gynecology and obstetrics, Emory School of Medicine, notes that experts already know that obesity is linked to cardiovascular disease, high blood pressure, diabetes, joint complications and other diseases. Now the connection between obesity and endometrial cancer is on experts’ radar.

Mary Dolan, MD, MPH

Mary Dolan, MD, MPH

Endometrial cancer forms in the tissue lining the uterus or endometrium – the lining that is “shed” monthly during menstruation. Endometrial cancer is more common in older women and fortunately is usually diagnosed early since it causes abnormal bleeding, says Dolan.

In a report published recently, Dolan and colleagues from the Centers for Disease Control and Prevention (CDC) discuss findings from a review of data from the Cancer and Steroid Hormone study from the 1980s. This study examined the relationship between oral contraceptive use and breast, ovarian and endometrial cancers in women ages 20-54 years.

Since many of the study patients with endometrial cancer were overweight, the study gave researchers an opportunity to look at the risk for endometrial cancer among younger, overweight women using BMI.

The study found that women who were younger than 45 when they had their last period and had a BMI over 35 had a 21.7 times greater risk of developing endometrial cancer than a woman of normal weight.

In comparison, older women with a BMI of 35 or higher, who had their last period at age 45 or older, had a 3.7 times greater risk of developing endometrial cancer than a woman of normal weight.

Elevated risks were also seen for women who had been overweight or obese at age 18 and who had their last period before age 45.

Dolan says obesity can lead to higher levels of estrogen because of chronic “anovulation,” where a woman fails to ovulate. Because the condition brings on irregular or no menstruation, estrogen levels remain high while opposing progesterone levels remain low. Experts believe this combination leads to an increased risk of endometrial cancer.

Dolan says physicians need to counsel patients even more to maintain a healthy weight. By both losing weight and then maintaining it, a woman’s risk for endometrial cancer likely decreases.

This study is one of only a few which have focused on younger women and the relationship between obesity and endometrial cancer. The results were published in the July 2009 issue of Obstetrics & Gynecology

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Pancreatic cancer: Front and center

With the sad news today of the death of actor Patrick Swayze, the public is again focused on pancreatic cancer and searching for more information on this aggressive cancer.

Recently, David Kooby, MD, Emory Winship Cancer Institute, and an assistant professor, Department of Surgical Oncology, authored a blog for the Atlanta Journal-Constitution’s “Doctor Is In” on this topic.

Emory Winship Cancer Institute

Emory Winship Cancer Institute

The following is an excerpt from the blog:

Pancreatic cancer is an aggressive malignancy that begins in the cells of the duct (or tube) running along the length of the pancreas. Each year about 42,000 new cases of pancreatic cancer are diagnosed and more than 35,000 people die from this cancer. A diagnosis of pancreatic cancer is usually made after discovery of a mass or a dilated duct in the pancreas.

Pancreatic cancer can be difficult to diagnose. Patients often come in for a doctor’s visit with non-specific symptoms such as abdominal or back pain or weight loss. Some patients will develop jaundice (yellowing of the skin) as a result of the tumor blocking the duct draining bile from the liver

No one knows the exact causes of pancreatic cancer, although some risk factors are known through research that has been done.

According to the National Cancer Institute, the following are risk factors for development of pancreatic cancer:

  • Age — The likelihood of developing pancreatic cancer increases with age. Most pancreatic cancers occur in people over the age of 60.
  • Smoking — Cigarette smokers are two or three times more likely than nonsmokers to develop pancreatic cancer.
  • Diabetes mellitus — Pancreatic cancer occurs more often in people who have diabetes than in people who do not.
  • Being male — More men than women are diagnosed with pancreatic cancer.
  • Being African-American — African-Americans are more likely than Asians, Hispanics or whites to get pancreatic cancer.
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