No junk: long RNA mimics DNA, restrains hormone responses

It arises from what scientists previously described as “junk DNA” or “the dark matter of the genome,” but this gene is definitely not junk. The gene Gas5 acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.

Unlike many genes scientists are familiar with, Gas5 does not encode a protein. It gets transcribed into RNA, like many other genes, but with Gas5 the RNA is what’s important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off.

Emory researchers have obtained a detailed picture of how the Gas5 RNA interacts with steroid hormone receptors. Their findings show how the Gas5 RNA takes the place of DNA, and give hints as to how it evolved.

The results were published Friday in Nature Communications.

Scientists used to think that much of the genome was “fly-over country”: not encoding any protein and not even accessed much by the cell’s gene-reading machinery. Recent studies have revealed that a large part of the genome is copied into lincRNAs (long intergenic noncoding RNAs), of which Gas5 is an example. Read more

Posted on November 7, 2014 by Quinn Eastman in Cancer, Immunology Leave a comment

Stop the blob!

For your viewing pleasure, we have two videos, courtesy of Winship Cancer Institute’s Adam Marcus.Â He and his colleagues are investigating whether Withania somnifera, a root used in Indian traditional medicine,Â could be a source for drugsÂ that inhibit breast cancer invasion and metastasis.Â Metastasis occurs when cells from a primary tumor migrate to a new location and invade the tissues at the new location.

The first video, the blob that grows, shows MCF10a mammary Ray Ban outlet epithelial cells undergoing epithelial-mesenchymal transition (EMT) in response to TGF-beta. This is a laboratory model for understanding breast cancer invasion and metastasis.

The second shows what happens when the same cells are treated with an extract from Withania somnifera. The blob doesn’t expand in such a threatening way anymore!Â The results were recently published in PLOS One.

Posted on October 16, 2013 by Quinn Eastman in Cancer Leave a comment

mTOR inhibitors gaining favor for breast cancer treatment

This week, breast cancer researchers have been reporting encouraging clinical trial results with the drug everolimus at the San Antonio Breast Cancer Symposium. Everolimus is a mTOR inhibitor, first approved by the FDA for treatment of kidney cancer and then for post-transplant control of the immune system.

Ruth O’Regan, MD, director of the Translational Breast Cancer Research Program at Winship Cancer Institute, has led clinical studies of everolimusÂ in breast cancerÂ and has championed the strategy of combining mTOR inhibitors with current treatments for breast cancer.

She recently explained the rationale to the NCI Cancer Bulletin:

She views the combination therapy as a potential alternative to chemotherapy for treating ER-positive advanced breast cancer when hormonal therapies have stopped working.

When resistance to hormonal therapies occurs, Dr. O’Regan explained, additional signaling pathways become activated. Unlike chemotherapy, which targets rapidly dividing cells, mTOR inhibitors are an example of the kind of treatment that may block growth-promoting signaling pathways.

Currently, Winship researchers are examining a combination involving everolimus and the EGFR inhibitor lapatinib for “triple-negative” breast cancer, a particularly aggressive and difficult-to-treat variety.

Posted on December 9, 2011 by Quinn Eastman in Cancer Leave a comment

Health Care Heroes honored by Atlanta Business Chronicle

Emory faculty-physicians were honored May 20 at the annual Health Care Heroes Awards celebration sponsored by the Atlanta Business Chronicle. All three are featured in this week’s edition of the newspaper.

Sheryl Gabram-Mendola, MD, professor of surgery at Emory School of Medicine and the Winship Cancer Institute, was the Community Outreach winner. Gabram-Mendola is director of the Avon Foundation Comprehensive Breast Center at the Georgia Cancer Center for Excellence at Grady Memorial Hospital.

She was nominated by the Georgia Cancer Coalition and honored for her work in reducing breast cancer mortality by increasing breast cancer awareness and leading the effort to diagnose the disease earlier in a high-risk population of minority women.

Last September the Avon Foundation awarded $750,000 to the Winship Cancer Institute at Emory and the Avon Comprehensive Breast Center. The grant is being used to continue community outreach, education, clinical access, and four research studies that directly affect care for the underserved populations in Atlanta. Since 2000, the Avon Foundation has awarded nearly $11 million to Winship and Grady to support leading-edge breast cancer research projects and improve outcomes for underserved women diagnosed with breast cancer in Atlanta.

Posted on May 21, 2010 by admin in Uncategorized Leave a comment

HER2-positive breast cancer treatment options studied

Emory oncologist Ruth O’Regan, MD, is leading a trial testing whether Afinitor can reverse resistance to Herceptin in metastatic HER2-positive breast cancer patients. As part of the trial, some patients been receiving a drug called Afinitor (everolimus) along with chemotherapy and Herceptin (trastuzumab).

Ruth O'Regan, MD

About 25 percent to 30 percent of breast cancers are HER2 -positive, which means they test positive for a protein called human epidermal growth factor receptor-2 (HER2). This protein promotes the growth of cancer cells, making HER2 -positive breast cancers more aggressive than other types.

They also tend to be less responsive to hormone treatment. That’s the bad news. The good news is that this type of cancer responds extremely well to Herceptin.

Herceptin specifically targets HER2 cells, killing them while sparing healthy cells, so side effects are minimal. Its effectiveness has made Herceptin the gold standard of treatment for HER2 -positive breast cancer.

Posted on April 20, 2010 by admin in Cancer Leave a comment

Looking at simple foods to protect against breast cancer

Researchers at the Winship Cancer Institute of Emory University have found that the hormone adiponectin may reduce the ability of cancer cells to migrate from the breast and invade other tissues. Adiponectin appears to protect against the effects of obesity on metabolism, the heart and blood vessels, the researchers say.

Fat cells make up most of the breast tissue, and some of the hormones produced by fat cells can have tumor-stimulating effects. Previous studies have shown that women with high body mass index (highest fifth) have double the death rate from breast cancer compared to those in the lowest fifth.

Dipali Sharma, PhD

The key to translating this research for patient care lies in finding a way to increase a person’s adiponectin, says Dipali Sharma, PhD, assistant professor of hematology and medical oncology at Winship.

Currently, Winship scientists are testing a molecule found in certain foods that appears to mimic the effects of adiponectin. The molecule is found in grapes, cabbage and green tea.

Posted on March 10, 2010 by admin in Cancer Leave a comment

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 Dâ€™Orsi, MD, FACR, director of the Emory Breast Imaging Center.

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. Some individuals may also consider including a breast ultrasound package for a more comprehensive screening approach.

Mammography is not a perfect test, but it has unquestionably been shown to save lives, says Dâ€™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

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 Dâ€™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.

Posted on November 24, 2009 by admin in Uncategorized 4 Comments

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 â€œcancer stem cellâ€ 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. Â 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 Â therapeutic agent will be able to target the cancer stem cells in for example all types brain tumors. Hence Â 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.Â

Winship’s director Brian Leyland-Jones has also reportedÂ 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

Posted on August 18, 2009 by Quinn Eastman in Cancer Leave a comment