"MASTER REGULATOR" Scientists find gene that controls proliferation of breast-cancer cells
WASHINGTON A common but hard-to-see type of lesion in the colon poses a stronger threat of cancer than the more frequently diagnosed colorectal polyps. Using colonoscopy data from patients, researchers in California found that the often undetected flat lesions could be 10 times more risky for colon cancer than the polyp-shaped neoplasms which are usually the target of colonoscopies. The discovery could push doctors to make greater efforts to detect and remove the flat lesions, called nonpolypoid colorectal neoplasms (NP-CRNs). "The current study emphasizes the importance of quality in the performance of colonoscopy," David Lieberman of the Oregon Health and Science University said in a commentary on the research. The current point of attack on colon cancer is to detect polyps and then remove them. But Roy Soetikno and colleagues at the Veterans Affairs Palo Alto Health Care System in California said their examinations of data for 1,819 patients who underwent colonoscopies found that 9.35 percent had NP-CRNs, and that the NP-CRNs were far more often cancerous than polyp-shaped lesions, whatever the relative size. "Overall, NP-CRNs were nearly 10 times more likely to contain cancerous tissue than polypoid lesions, irrespective of the size," a summary of their research said. "Future studies on NP-CRNs should further evaluate whether the diagnosis and removal of NP-CRNs has any effect on the prevention and mortality of colorectal cancer and particularly focus on their genetic and protein abnormalities," Soetikno and his team concluded. Lieberman added that more work needs to be done on the imaging from colonoscopies to better detect the NP-CRNs and to see whether patients with these types of lesions require more intense colonoscopic tests. The research and Lieberman's comments were published in the March 5 edition of the Journal of the American Medical Association.
WASHINGTON More than one in three group-based cancer trials used a flaw statistical methodology to study the effects of an intervention, according to a study that reviewed 75 articles in 41 medical journals from 2002 to 2006. The review found that 34 articles or 45 percent used "appropriate" methods to analyze the results of trials of randomly picked individuals, while 26 articles or 35 percent used "inappropriate" methodology, the researchers said in the Journal of the National Cancer Institute. "We cannot say any specific studies are wrong. We can say that the analysis used in many of the papers suggests that some of them probably were overstating the significance of their findings," said lead author David Murray, chair of epidemiology in the College of Public Health at Ohio State University. Eight percent of reviewed articles used a combination of appropriate and inappropriate methods while nine articles did not have enough information to judge if the methodology was appropriate or not, the researchers said. Of the studies that used inappropriate methods, 88 percent reported statistically significant intervention effects that could be misleading to scientists and policy-makers due to analysis flaws, the reviewers said. "In science, generally, we allow for being wrong five percent of the time," Murray said. "If you use the wrong analysis methods with this kind of study, you might be wrong half the time. We're not going to advance science if we're wrong half the time." But he emphasized that the studies did not willfully use inappropriate methods or try to skew results of a trial. Murray and his colleagues urged researchers to collaborate with statisticians familiar with studies of groups in which individuals are randomly chosen. "Am I surprised by these findings? No, because we have done reviews in other areas and have seen similar patterns," Murray said. "It's not worse in cancer than anywhere else, but it's also not better. What we're trying to do is simply raise the awareness of the research community that you need to attend to these special problems that we have with this kind of design."
PARIS Geneticists have identified a super gene that causes breast cancer to metastasize. Described as a "master regulator," the SATB1 gene alters the behavior of at least 1,000 other genes within tumor cells, said the study published in Nature. When overactivated it makes cancer cells proliferate, and when neutralized the gene stops the cells from dividing and migrating, the study reported. "SATB1will be a remarkable target for cancer therapy," said lead scientist Termumi Kohwi-Shigematsu of the Lawrence Berkeley National Laboratory in Berkeley, California. The findings could not only pave the way to diagnostic tools that show the likelihood of the disease spreading, she said, but to drugs that could prevent or treat metastasis in breast cancer as well. Up to now, it was impossible to predict whether cancer cells in a tumor were destined to invade neighboring tissue, travel through the blood system, and form secondary tumors elsewhere in the body. But the SATB1 protein is just such a marker. A tumor in which it is activated "is destined to metastasize," said Kohwi-Shigematsu. Metastasis is the overwhelming cause of death in patients with solid tumors. Less than 10 percent of women with metastatic breast cancer survive beyond a decade, and just over a quarter make it past five years. SATB1's normal role in organizing other genes-especially related to T-cells that play a critical role in the immune system-was already well known, thanks in part to pioneering research by Kohwi-Shigematsu in the 1990s. The gene had also been identified in breast tumors. But the new study is the first to establish that SATB1 is both necessary and sufficient for breast-cancer cells to become metastatic," she said. In experiments on mice, Kohwi-Shigematsu and colleagues "knocked down" or deactivated the SATB1 gene by removing certain RNAs in the tumor cells upon which the gene depends for multiplying. Messenger RNAs are tiny strings of nucleotides-the basic building blocks of DNA-that ferry the blueprints for constructing proteins from DNA genes to the cell's ribosomes, the factories where proteins are made. The results, compared to those in control mice also infected with human metastatic breast-cancer cells, were dramatic. Between 125 and 160 metastatic nodules formed in each lung of all the control mice. But in the rodents in which SATB1was suppressed, the number was between zero and five. Deliberately overexpressing the gene had the opposite effect, causing the cancer cells to rapidly reproduce and run amok. Translating the study's findings into an effective treatment for cancer would require targeting only the tumors in which the SATB1gene has become overly active. A drug that blocked the gene throughout the body would compromise its critical-and normal-role in activating the immune system. Kohwi-Shigematsu is working on a means for delivering an inhibitor via microscopic nanocapsules, and said trials on humans could start within a couple of years. Prognostic tools could be available within a year. Kohwi-Shigematsu's research is part of a new wave of cancer studies focusing on the genetic origins of the disease. Scientists have come to realize that there are gene expression patterns called prognosis signatures, genetic profiles found across primary tumors that have metastatic potential, she said. "And now we have identified the protein master regulator for metastasis." But the most basic question remains to be answered, she added. "What turns SATB1on during the course of breast-cancer progression? We just don't know."
SYDNEY Highly aggressive breast cancers might in the future be "put to sleep" rather than attacked with chemotherapy, research by an Australian scientist suggests. Dr. Alex Swarbrick of Sydney's Garvan Institute said the research, conducted in collaboration with US-based Nobel Prize winning Prof. J. Michael Bishop, found that a gene called Id1 drives some breast cancers. But by switching the gene on and off, it was possible to either encourage or shrink tumors. In experiments with mice, Swarbrick found that by stimulating the gene he could create tumors. Moreover, mammary cancers with high levels of the gene became very aggressive and were likely to spread to the rest of the body. "We also showed that if we genetically switch off the Id1 gene in an established tumor, those mice live much longer than mice with continual Id1 expression in their tumor," he said. "In fact, about 40 percent of them were cured and the tumors just shrank away." Swarbrick said the findings, published in the Proceedings of the National Academy of Sciences, suggested that as well as trying to kill cancer cells, doctors could also try to put breast tumors to sleep. "Many cancers mutate the genes involved in cell death, so it's hard to kill them," he said. The research results suggested that by therapeutically targeting genes that could switch off the cancers, such as Id1, tumors could be put to sleep, he said. "You induce a terminal sleep, and then the immune system just gobbles them up."
WASHINGTON Scientists have perfected a new technique to magnify by more than 1,000 times molecules deep inside the human body, which may help detect miniscule tumors. The technique of noninvasive molecular imaging of small subjects uses a phenomenon known as Raman spectroscopy, and the research team from Stanford University School of Medicine believes it is the first such study of its kind. "This is an entirely new way of imaging living subjects, not based on anything previously used," said lead author Sanjiv Sam Gambhir. The new imaging system can show up tumors, using tiny nanoparticles injected into the body to serve as scientific beacons as they attach themselves to different tumor molecules. Raman spectroscopy is a phenomenon first discovered in the 1920s by an Indian doctor and refers to the scattering that happens when light from a source such as a laser is shone on an object. The technique is largely used in industry and research, and measures the way that the light hits the object and bounces off again. The scattering pattern that is created is known as a spectral fingerprint, and is unique to each kind of molecule, helping to determine a material's molecular composition and structure. The Stanford team believes this is the first time the technique has been adapted to provide images from inside the human body. The signals emitted by spectroscopy are stronger and last longer than those of other available methods, and could provide information about various molecules all at the same time, said Gambhir. "Usually we can measure one or two things at a time," he said. "With this, we can now likely see 10, 20, 30 things at once." And these specialized particles emit signals that can be measured and then converted into a visible location in the body. "The imaging modality reported here holds significant potential as a strategy for biomedical imaging of living subjects," Gambhir wrote in the study published in the Proceedings of the National Academy of Sciences. The technique could prove useful in surgery for removing cancerous tissue, as the imager is so sensitive it can aid doctors in finding even the smallest amount of malignant cells, he added. Gambhir compared the team's work to the development of the positron emission tomography (PET) discovered some three decades ago, which has become a routine imaging technique for cancer detection by creating a three-dimensional image of what is happening inside the body. "Nobody understood the impact of PET then. Ten or 15 years from now, people should appreciate the impact of this," he said. The team's first tests were carried out on mice, and a clinical trial is now planned on humans using gold nanoparticles for possible use with a colonoscopy for the early detection of colon cancer. M |
