Two 'noses' are necessary for flies to navigate well
Animals and insects communicate through an invisible world of scents. By exploiting infrared technology, researchers at Rockefeller University just made that world visible. With the ability to see smells, these scientists now show that when fly larvae detect smells with both olfactory organs they find their way toward a scented target more accurately than when they detect them with one.
"Having two eyes allows us to have depth perception and two ears allows us to pinpoint a noise precisely,” says Leslie Vosshall, head of the Laboratory of Neurogenetics and Behavior. "Sensing odors in stereo is equally important.”
In research to be published in the December 23 online issue of Nature Neuroscience, Vosshall and her colleagues show that odor information is easier to perceive when it is smelled with both olfactory organs. By genetically manipulating flies to express odorant receptors in one olfactory organ or both, they show that the brains of Drosophila melanogaster larvae not only make use of stereo cues to locate odors but also to navigate toward them — a behavior called chemotaxis.
To study this behavior, Vosshall and her colleagues had to figure out which direction the larvae move with respect to the source of the odor. But since odors are invisible, the researchers could neither predict how the flies would move in relation to these scents nor guess whether the odors were concentrated in patches or along a gradient. To complicate matters, odors whisk to and fro at the mercy of the slightest stir, making it impossible to determine their concentrations at particular locations.
"We needed to create an environment in which we knew something about the spatial arrangement of the odors,” says Vosshall. "We needed to see the smells.”
In collaboration with colleagues in Thomas P. Sakmar’s Laboratory of Molecular Biology and Biochemistry, the researchers used a novel spectroscopic technique that exploited infrared light to create environments where they could see, control and precisely quantify the distribution of these smells.
When Vosshall and her colleagues observed the animals’ behavior, they found that although animals with one functional nose or two were both able to sense odors, only the ones with both olfactory organs working accurately navigated toward the odor source. "A left-right comparison isn’t necessary for flies to smell,” says Vosshall, "but it is necessary for them to do it well.”
Chemotherapy and tamoxifen reduce risk of second breast cancer
Among breast cancer patients, both chemotherapy and tamoxifen independently reduced the risk of developing a second cancer in the other breast, according to a study published online December 25 in the Journal of the National Cancer Institute. The risk reduction persisted for at least 10 and 5 years, respectively.
For breast cancer patients the risk of developing cancer in the other breast is two to six times greater than the breast cancer risk of the general public. Studies have shown that taking tamoxifen for five years reduces the risk of cancer in the opposite breast among women who have estrogen receptor-positive breast cancer, but the studies did not clarify how long the protective effect lasts.
Lisbeth Bertelsen, M.D., of the Danish Cancer Society in Copenhagen and colleagues investigated the relationship between tamoxifen and chemotherapy—either alone or in combination—and the risk of cancer in the opposite breast among American and Danish women who were first diagnosed with breast cancer before age 55. The study included 1,158 women who developed cancer in one breast and an additional 634 who initially had cancer in one breast then developed a second cancer in the other breast.
The chemotherapy treatment was associated with a 43 percent reduced risk for developing cancer in the opposite breast, compared with no chemotherapy. This risk reduction lasted up to 10 years after the initial cancer diagnosis and was stronger among women who entered menopause within a year of their diagnosis. Tamoxifen use was associated with a 34 percent reduced risk of a second breast cancer, compared with no tamoxifen use, and this reduction continued for five years after diagnosis.
"Ovarian suppression caused by chemotherapy may have a role in the association, possibly in combination with a cytotoxic effect on [breast tumor cells],” the authors write.
Anthracyclines improve survival in HER2-positive breast cancer patients
Treatment with the class of chemotherapy drugs called anthracyclines improves survival in women with HER2-positive breast cancer who have previously had surgery, but it may not offer any benefit for women with HER2-negative tumors, according to a study published online December 25 in the Journal of the National Cancer Institute.
Randomized clinical trials have demonstrated that treating early breast cancer with anthracycline-based chemotherapy improves disease-free and overall survival rates more than non-anthracycline-based regimens. However, the studies have demonstrated that anthracyclines may slightly increase the risk of heart damage and leukemia. Given these side effects, the greatest benefit of these regimens may be in women with breast tumors that overexpress HER2—a gene that is often amplified in tumors that respond to anthracyclines.
Alessandra Gennari, M.D., Ph.D., of the National Cancer Research Institute in Genoa, Italy, and colleagues compiled data from eight randomized controlled trials that compared anthracyclines and non-anthracyclines, and also reported HER2 status. Almost 30 percent of the patients’ tumors overexpressed HER2.
Overall and among patients with HER2-positive tumors, anthracycline-based chemotherapy produced a greater reduction in the risk of relapse or death than non-anthracycline-based regimens. However, among patients with HER2-negative tumors, there was no difference in survival between the chemotherapy regimens.
"The absence…of any effect of anthracyclines observed in patients with HER2-negative disease suggests that this group of patients could be spared unnecessary toxic effects related to the use of this class of agents and raises questions as to the appropriateness of control arms in randomized clinical trials in which anthracycline-based regimens are used in unselected patient populations,” the authors write.
In an accompanying editorial, Soonmyung Paik, M.D., of the National Surgical Adjuvant Breast and Bowel Project in Pittsburgh and colleagues point out that HER2 status alone may not be enough to determine who should receive anthracyclines, given the molecular differences among different subtypes of breast cancer.
"Optimization of adjuvant chemotherapy for patients diagnosed with breast cancer will depend on defining the baseline prognosis and chemosensitivity of each subclass of breast cancer beyond those crudely defined by HER2 status alone,” the editorialists write.
Varying prevalence among ethnic groups of gene mutation that increases risk of breast cancer
CHICAGO – Among several U.S. racial/ethnic groups examined, Hispanic women were found to have the highest prevalence of the cancer-associated gene mutation BRCA1 at 3.5 percent, with Asian Americans having the lowest prevalence (0.5 percent), according to a study in the December 26 issue of JAMA.
Mutations in the tumor suppressor gene BRCA1 confer high risks of breast and ovarian cancer. Average cumulative risk by age 70 years has been estimated at 65 percent for breast cancer and 39 percent for ovarian cancer, according to background information in the article. Although mutations in BRCA1 are rare, they are more frequently present in individuals with multiple relatives having breast or ovarian cancer, early-onset breast cancer, or of Ashkenazi Jewish ancestry. Information on the prevalence of BRCA1 mutation carriers in racial/ethnic minority populations is limited.
Esther M. John, Ph.D., of the Northern California Cancer Center, Fremont, Calif., and colleagues examined the prevalence of BRCA1 mutations in Hispanic, African American and Asian American female breast cancer patients compared with non-Hispanic white patients with and without Ashkenazi Jewish ancestry. The patients, younger than 65 years at diagnosis, were enrolled at the Northern California site of the Breast Cancer Family Registry (n = 3,181) during the period 1996-2005.
In patients without reported Ashkenazi Jewish ancestry, estimated mutation prevalence was highest in Hispanic patients (3.5 percent), followed by non-Hispanic white patients (2.2 percent), African American patients (1.3 percent), and Asian American patients (0.5 percent). Those with Ashkenazi Jewish ancestry had a prevalence of 8.3 percent. Within each racial/ethnic group, prevalence estimates decreased with age at diagnosis and were higher in patients who reported a family history of breast or ovarian cancer than in those who did not.
The prevalence of BRCA1 mutations was particularly high in African American patients diagnosed before age 35 years (16.7 percent), compared with young Hispanics (8.9 percent), non-white Hispanics without Ashkenazi Jewish ancestry (7.2 percent), and Asian Americans (2.4 percent).
"The present study included multiple racial/ethnic groups, therefore allowing direct comparison of carrier prevalence estimates. Since certain mutations may be unique to specific populations, the full spectrum of mutations needs to be determined. Such information may facilitate mutation screening in a clinical setting and is needed to guide resource allocation for genetic testing, genetic counseling, and planning of preventive interventions in all population subgroups,” the authors conclude.
(JAMA. 2007;298(24):2869-2876. Available pre-embargo to the media at www.jamamedia.org)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Genetic Testing in Diverse Populations - Are Researchers Doing Enough to Get Out the Correct Message?
In an accompanying editorial, Dezheng Huo, M.D., Ph.D., and Olufunmilayo I. Olopade, M.D., of the University of Chicago, comment on the findings regarding genetic testing for BRCA1.
"As documented by John et al, more than half of BRCA1 mutation carriers would be detected in female patients with breast cancer whose cancers are likely to be hereditary based on age at diagnosis and family history. The differences in BRCA1 mutation prevalence across populations should be used to more accurately calculate the pretest probability of having a mutation, rather than as evidence against genetic testing in minority populations. While there has been great debate about the role of race/ethnicity in health research, clinicians interested in providing patients with personalized assessment of cancer risk must understand the contributions of BRCA1 and BRCA2 mutations in diverse populations, because potential modifying factors particular to patients’ race/ethnicity, family history, ancestral country of origin, and environmental factors may work in concert to influence outcomes.”
(JAMA. 2007;298(24):2910-2911. Available pre-embargo to the media at www.jamamedia.org)
Neglected tropical diseases burden those overseas, but travelers also at risk
Though little known to most Americans, lymphatic filariasis, trachoma, leishmaniasis, onchocerciasis, schistosomiasis and other so-called neglected tropical diseases are responsible for severe health burdens, especially among the world’s poorest people. Together, it is estimated that these illnesses, most of which are caused by worms or other parasites, rank sixth among all conditions worldwide in robbing people of quality of life and life itself through disability or premature death, respectively. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has a long-standing, robust program of research and clinical trials devoted to better understanding and combating neglected tropical diseases, most notably those caused by parasites. In 2006, NIAID devoted $117 million to these projects, which are carried out both in the United States and in countries where the diseases are endemic.
While most sufferers of neglected tropical diseases reside permanently in tropical regions, Americans and other travelers to such areas may also be exposed to these disease-causing organisms. To better gauge illnesses following travel to the tropics and subtropics, the GeoSentinel Surveillance Network, a network of travel/tropical medicine clinics on six continents, was established in 1995. A new paper by NIAID scientist Thomas Nutman, M.D., and colleagues reviews network data collected between 1997 and 2004 to determine demographic and travel characteristics of travelers diagnosed with parasitic worm (filarial) infections. The researchers found that filarial infections responsible for such diseases as onchocerciasis (river blindness), lymphatic filariasis (elephantiasis) and loiasis (African eyeworm illness) made up 271 (0.62 percent) of the 43,722 medical conditions reported to the network during that time period. Additionally, the data showed that immigrants from filarial-endemic regions were most likely to come to the travel/tropical diseases clinics, and that long-term travel of more than one month was more likely to be associated with filarial infection than were shorter trips. The most commonly acquired filarial infection (37 percent) was Onchocerca volvulus, the worm that causes river blindness.
While clinical presentation of filarial disease is known to differ between visitors to and natives of endemic regions, this new analysis provides a quantitative assessment of the characteristics of those who acquire filarial infections following travel. Furthermore, the information collected by the GeoSentinel network can be used to assess not only acute but also chronic infections. Ultimately, the authors write, these data will provide a comprehensive backdrop to pre-travel advice and post-travel treatment for those at risk of acquiring a filarial infection.
Poor Americans in the United States suffer hidden burden of parasitic and other neglected diseases
Large numbers of the poorest Americans living in the United States are suffering from some of the same parasitic infections that affect the poor in Africa, Asia, and Latin America, says the Editor-in-Chief of PLoS Neglected Tropical Diseases.
In an article entitled "Poverty and Neglected Diseases in the ‘Other’ America,” Professor Peter Hotez (George Washington University and the Sabin Vaccine Institute) says that there is evidence that the parasitic diseases toxocariasis, cysticercosis and toxoplasmosis as well as other neglected infections are very common in the United States, especially among poor and underrepresented minority populations living in inner cities and poor rural areas. Such infections are known as neglected tropical diseases (NTDs) because they afflict mostly poor people and are often ignored by public health officials and political leaders despite their enormous medical importance.
Toxocariasis, caused by the roundworm Toxocara canis, is now a common parasitic infection among inner city African-American and Hispanic children. Possibly as many as 23% of Americans living in poverty are exposed to this parasitic worm, in whom it causes a lung disease that resembles asthma, as well as liver and brain disease. Cysticercosis, caused by the tapeworm Taenia solium, is emerging as the leading cause of epilepsy among Hispanic populations in the US, and toxoplasmosis is an important cause of congenital birth defects among Mexican Americans and African Americans.