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Archive - 2012

November 5th

Second Species of Mole Rat Has Different Anti-Cancer Mechanism

Biologists at the University of Rochester have determined how blind mole rats fight off cancer—and the mechanism differs from what they discovered three years ago in another long-lived and cancer-resistant mole rat species, the naked mole rat. The team of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, found that abnormally growing cells in blind mole rats secrete the interferon beta protein, which causes those cells to rapidly die. Drs. Seluanov and Gorbunova hope the discovery will eventually help lead to new cancer therapies in humans. Their findings were published November 5, 2012 in PNAS. Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only mammals never known to develop cancer. Three years ago, Drs. Seluanov and Gorbunova determined the anti-cancer mechanism in the naked mole rat. Their research found that a specific gene—p16—makes the cancerous cells in naked mole rats hypersensitive to overcrowding, and stops them from proliferating when too many crowd together. "We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous cells," said Dr. Seluanov. "Instead, we discovered they've evolved their own mechanism." Drs. Gorbunova and Seluanov made their discovery by isolating cells from blind mole rats and forcing them to proliferate in culture beyond what occurs in the animal. After dividing approximately 15-20 times, all of the cells in the culture dish died rapidly. The researchers determined that the rapid death occurred because the cells recognized their pre-cancerous state and began secreting a suicidal protein, called interferon beta.

November 4th

Exome Sequencing Identifies Novel Genes That May Drive Rare, Aggressive Form of Uterine Cancer

Researchers have identified several genes that are linked to one of the most lethal forms of uterine cancer, serous endometrial cancer. The researchers describe how three of the genes found in the study are frequently altered in the disease, suggesting that the genes drive the development of tumors. The findings appear in the October 28, 2012 advance online issue of Nature Genetics. The team was led by researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. Cancer of the uterine lining, or endometrium, is the most commonly diagnosed gynecological malignancy in the United States. Also called endometrial cancer, it is diagnosed in about 47,000 American women and leads to about 8,000 deaths each year. Each of its three major subtypes — endometrioid, serous, and clear-cell —is caused by a different constellation of genetic alterations and has a different prognosis. Endometrioid tumors make up about 80 percent of diagnosed tumors. Surgery often is a complete cure for women with the endometrioid subtype, because doctors usually diagnose these cases at an early stage. Compared to other subtypes, the 2 to 10 percent of uterine cancers that comprise the serous subtype do not respond well to therapies. The five-year survival rate for serous endometrial cancer is 45 percent, compared to 65 percent for clear-cell and 91 percent for endometrioid subtypes. Serous and clear-cell endometrial tumor subtypes are clinically aggressive and quickly advance beyond the uterus. "Serous endometrial tumors can account for as much as 39 percent of deaths from endometrial cancer," said Daphne W. Bell, Ph.D., an NHGRI investigator and the paper's senior author. Dr. Bell heads the Reproductive Cancer Genetics Section of NHGRI's Cancer Genetics Branch.

November 4th

New Method Empowers Fluorescent Technology

The ability of fluorescence microscopy to study labeled structures like cells has now been empowered to deliver greater spatial and temporal resolutions that were not possible before, thanks to a new method developed by Beckman Institute faculty member Dr. Gabriel Popescu and Dr. Ru Wang from his research group. Using this method, the researchers were able to study the critical process of cell transport dynamics at multiple spatial and temporal scales and reveal, for the first time, properties of diffusive and directed motion transport in living cells. Dr. Popescu leads the Quantitative Light Imaging Laboratory at Beckman, while Dr. Wang of the lab is first author on the paper reporting the method online on November 2, 2012 in Physical Review Letters. The new approach, called dispersion-relation fluorescence spectroscopy (DFS), labels molecules of interest with a fluorophore whose motion, the researchers write, “gives rise to spontaneous fluorescence intensity fluctuations that are analyzed to quantify the governing mass transport dynamics. These data are characterized by the effective dispersion relation.” That ability to study the directed and diffusive transport characteristics of cellular dispersion through a wide range of temporal and spatial scales is more comprehensive than using just fluorescence microscopy. It provides more information than existing methods, such as fluorescence correlation spectroscopy (FCS), which is widely used for studying molecular transport and diffusion coefficients at a fixed spatial scale.

New Means to Kill Malaria Parasiste

Malaria causes up to 3 million deaths each year, predominantly afflicting vulnerable people such as children under five and pregnant women, in tropical regions of Africa, Asia, and Latin America. Treatments are available for this disease, but the Plasmodium parasite is fast becoming resistant to the most common drugs, and health authorities say they desperately need new strategies to tackle the disease. This new potential treatment uses molecules that interfere with an important stage of the parasite's growth cycle and harnesses this effect to kill them. The impact is so acute it kills ninety per cent of the parasites in just three hours and all those tested in laboratory samples of infected human blood cells, within twelve hours. The research was carried out by chemists at Imperial College London and biological scientists from the research institutions Institut Pasteur and CNRS in France. Their work was published in the the October 9, 2012 issue of PNAS. Lead researcher Dr. Matthew Fuchter, from Imperial College London, said: "Plasmodium falciparum causes 90 per cent of malaria deaths, and its ability to resist current therapies is spreading dramatically. Whilst many new drugs are in development, a significant proportion are minor alterations, working in the same way as current ones and therefore may only be effective in the short term. We believe we may have identified the parasite’s 'Achilles' Heel, using a molecule that disrupts many vital processes for its survival and development." The research has identified two chemical compounds that affect Plasmodium falciparum's ability to carry out transcription, the key process that translates genetic code into proteins. These compounds are able to kill the parasite during the long period of its complex life cycle while it inhabits the blood-stream.

Whitehead Scientists Identify Major Flaw in Standard Approach to Global Gene Expression Analysis

Whitehead Institute researchers report that common assumptions employed in the generation and interpretation of data from global gene expression analyses can lead to seriously flawed conclusions about gene activity and cell behavior in a wide range of current biological research. "Expression analysis is one of the most commonly used methods in modern biology," says Whitehead Member Dr. Richard Young. "So we are concerned that flawed assumptions may affect the interpretation of many biological studies." Much of today's interpretation of gene expression data relies on the assumption that all cells being analyzed have similar total amounts of messenger RNA (mRNA), the roughly 10% of a cell's RNA that acts as a blueprint for protein synthesis. However, some cells, including aggressive cancer cells, produce several times more mRNA than other cells. Traditional global gene expression analyses have typically ignored such differences. "We've highlighted this common assumption in gene expression analysis that potentially affects many researchers," says Dr. Tony Lee, a scientist in Dr. Young's lab and a corresponding author of the article published in the October 26, 2012 issue of Cell. "We provided a concrete example of the problem and a solution that can be implemented by investigators." Members of the Dr. Young lab recently uncovered the flaw while investigating genes expressed in cancer cells expressing high levels of c-Myc, a gene regulator known to be highly expressed in aggressive cancer cells. When comparing cells with high and low c-Myc levels, they were surprised to find very different results using different approaches to gene expression analysis.

November 3rd

New Clues for Overcoming Tamoxifen-Resistant Breast Cancer

A University of Cincinnati (UC) cancer biology team reports breakthrough findings about specific cellular mechanisms that may help overcome endocrine (hormone) therapy-resistance in patients with estrogen-positive breast cancers, combating a widespread problem in effective medical management of the disease. Xiaoting Zhang, Ph.D., and his colleagues have identified a specific estrogen receptor co-activator—known as MED1—as playing a central role in mediating tamoxifen resistance in human breast cancer. The team reported its findings online in the Nov. 1, 2012, issue of Cancer Research, a scientific journal of the American Association for Cancer Research. According to the National Cancer Institute, nearly 227,000 women are diagnosed with breast cancer annually in the United States. About 75 percent have estrogen-positive tumors and require adjuvant hormone therapy such as tamoxifen, a drug that works by interfering with estrogen’s ability to stimulate breast cancer cell growth. Despite advances in hormone therapy drugs, cancer surveillance research has shown that 50 percent of patients will develop resistance to the drug and experience a cancer relapse. The hormones estrogen and progesterone can stimulate the growth of some breast cancers. Hormone therapy is used to stop or slow the growth of these tumors. Hormone-sensitive (i.e., positive) breast cancer cells contain specific proteins known as hormone receptors that become activated once hormones bind to them, leading to cancer growth. Based on new findings, UC Cancer Institute scientists believe that tamoxifen resistance may be driven by a novel molecular "crosstalk” point between the estrogen and HER2 (human epidermal growth factor receptor 2) signaling pathways.

Multicenter Team Identifies Promising Treatment for Polycystic Kidney Disease

A drug therapy shows promise for treating an inherited form of kidney disease called autosomal dominant polycystic kidney disease (ADPKD), Mayo Clinic researchers say. The medication, tolvaptan, slowed the pace of kidney cyst growth over the three years of the study. The phase three clinical trial results were being presented on November 3, 2012 at the American Society of Nephrology annual meeting and published online in the New England Journal of Medicine. The multicenter study found tolvaptan demonstrated a nearly 50 percent reduction in the rate of increase in total kidney volume (a measurement of kidney cyst growth) in ADPKD patients over the study period, compared to placebo. "ADPKD is the most common inherited and the fourth most common overall cause of kidney failure worldwide," says lead author Vicente Torres, M.D., Ph.D., Mayo Clinic nephrologist. "In most patients with this disease, relentless cyst growth within the kidneys destroys the tissue, causes hypertension and painful complications, and negatively impacts the quality of life," Dr. Torres says. "The results of this study reveal a potential treatment that blunts kidney growth, lessens associated symptoms, and slows kidney function decline when given over three years." While the trial findings are encouraging, tolvaptan has not yet been approved for this indication, Dr. Torres notes. [Press release] [New England Journal of Medicine]

October 24th

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Plants Provide Accurate, Low-Cost Alternative for Diagnosis of West Nile Virus

Dr. Qiang “Shawn” Chen, a researcher at Arizona State University’s Biodesign Institute and a professor in the College of Technology and Innovation has developed a new method of testing for West Nile virus (WNV), using plants to produce biological reagents for detection. While the United States has largely been spared the scourge of mosquito-borne diseases endemic to the developing world—including yellow fever, malaria, and dengue fever—mosquito-related illnesses in the US are on the rise. One pathogen of increasing concern in the U.S. is an arbovirus known as West Nile. The new research, conducted by Dr. Chen and his colleagues at the Center for Infectious Diseases and Vaccinology was published, in open-access full text, in the Journal of Biomedicine and Biotechnology. “One critical issue in WNV diagnosis concerns the difficulty of distinguishing WNV infection from other closely related diseases, such as St. Louis encephalitis and dengue fever, due to the cross-reactivity of antibodies among flaviviruses,” Dr. Chen says. “It is important to develop better diagnostic tools with enhanced accuracy for both treatment and diagnostic purposes.” Thus far, the 2012 outbreak of West Nile in the United States is on track to be one of the worst on record. According to the Center for Disease Control, 48 states have reported WNV infections in people, birds, or mosquitoes as of October 9th of this year. To date, 4,249 cases of WNV disease have been reported in humans, including 168 deaths. Of these cases 2,123 (50 percent) appeared in the more severe or neuroinvasive form of the disease, causing meningitis and encephalitis, while 2,126 cases were classified as non-neuroinvasive.

October 24th

12-Gene Chemokine Signature May Be Associated with Better Survival in Metastatic Melanoma

Researchers at the Moffitt Cancer Center in Tampa, Florida have discovered a unique immune gene signature that can predict the presence of microscopic lymph node-like structures in metastatic melanoma. The presence of these immune structures, the researchers said, appears to be associated with better survival and may indicate the possibility of selecting patients for immunotherapy based solely on the immune-related makeup of their tumors as an approach to personalized medicine. The full text of the study appeared online on October 24, 2012 in Scientific Reports, a journal from the Nature Publishing Group. In this study, the researchers analyzed a 12-chemokine gene expression signature across nearly 15,000 distinct solid tumors of different types, including metastatic melanoma. Chemokines are powerful immune system molecules known to be important in lymph node formation and function during development. The 12-chemokine gene expression signature was found to remarkably predict the presence of microscopic lymph node-like structures within some melanomas and was also associated with better overall survival of these patients. The researchers speculate that the lymph nodal structures they identified are active and playing an important positive role in a self-elicited (endogenous) anti-tumor response – initially locally and then systemically. They also anticipate that their findings in melanoma may extend to other solid tumors, such as those of colorectal, lung, and ovarian origin.