Posts Tagged Diseases and Conditions

Tumor cells’ inner workings predict cancer progression


ScienceDaily (July 27, 2012) — Using a new assay method to study tumor cells, researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center have found evidence of clonal evolution in chronic lymphocytic leukemia (CLL). The assay method distinguishes features of leukemia cells that indicate whether the disease will be aggressive or slow-moving, a key factor in when and how patients are treated.

The findings are published in the July 26, 2012 First Edition online issue of Blood.

The progression of CLL is highly variable, dependent upon the rate and effects of accumulating monoclonal B cells in the blood, marrow, and lymphoid tissues. Some patients are symptom-free for years and do not require treatment, which involves the use of drugs that can cause significant side effects and are not curative. In other patients, however, CLL is relatively aggressive and demands therapeutic intervention soon after diagnosis.

“Our study shows that there may not be a sharp dividing line between the more aggressive and less aggressive forms of CLL,” said Thomas J. Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research and senior author of the study. “Instead, it seems that over time the leukemia cells of patients with indolent disease begin to use genes similar to those that are generally used by CLL cells of patients with aggressive disease. In other words, prior to requiring therapy, the patterns of genes expressed by CLL cells appear to converge, regardless of whether or not the patient had aggressive versus indolent disease at diagnosis.”

Existing markers for aggressive or indolent disease are mostly fixed and have declining predictive value the longer the patient is from his or her initial diagnosis. When the blood sample is collected, these markers cannot reliably predict whether a CLL patient will need therapy soon, particularly when the patient has had the diagnosis of CLL for many years.

Kipps and colleagues studied thousands of genes, particularly those that code for proteins, in a group of 130 CLL patients with varying risks of disease progression. They identified 38 prognostic subnetworks of interacting genes and proteins that, at the time of sample collection, indicate the relative the aggressiveness of the disease and predict when the patient will require therapy. They confirmed their work using the method on two other, smaller CLL patient cohorts in Germany and Italy.

The subnetworks offer greater predictive value because they are based not on expression levels of individual genes or proteins, but on how they dynamically interact and change over time, influencing the course of the CLL and patient symptoms.

“In a sense, we looked at families rather than individuals,” said Kipps. “If you find in an interconnected family where most genes or proteins are expressed at higher levels, it becomes more likely that these genes and proteins have functional significance.”

He added that while the subnetworks abound in data, their complexity actually makes them easy to interpret and understand. “It’s like when you look out of a window and see the sky, clouds, trees, people, cars. You’re getting tremendous amounts of information that individually doesn’t tell you much. But when you look at the scene as a whole, you see patterns and networks. This work is similar. We’re taking all of the individual gene expression patterns and making sense of them as a whole. We’re more able to more clearly see how they control and regulate function.”

The findings help define how CLL — and perhaps other cancers — evolve over time, becoming more aggressive and deadly. “It’s as if each tumor has a clock which determines how frequently it may acquire the chance changes that make it behave more aggressively. Although the rates can vary, it appears that tumors march down similar pathways, which converge over time to a point where they become aggressive enough to require therapy.”

The study may alter how scientists think about CLL and how clinicians treat the disease: whether it is better to wait for later stages of the disease when tumor cells are more fragile and easier to kill, or treat early-stage indolent tumor cells aggressively, when they are fewer in number but harder to find and more resistant to therapy.

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The above story is reprinted from materials provided by University of California – San Diego, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Han-Yu Chuang, Laura Rassenti, Michelle Salcedo, Kate Licon, Alexander Kohlmann, Torsten Haferlach, Robin Foà, Trey Ideker, and Thomas J. Kipps. Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression. Blood, July 26, 2012 DOI: 10.1182/blood-2012-03-416461

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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CT angiography speeds emergency diagnosis of heart disease in low-risk patients


ScienceDaily (July 25, 2012) — Incorporating coronary CT angiography (CCTA) into the initial evaluation of low-risk patients coming to hospital emergency departments (EDs) with chest pain appears to reduce the time patients spend in the hospital without incurring additional costs or exposing patients to significant risks. The report of a study conducted at nine U.S. hospitals appears in the July 26 New England Journal of Medicine.

“We found that the use of CCTA in emergency department evaluation of acute chest pain very effectively identified which patients did or did not have coronary artery obstruction, allowing clinicians to focus the use of resources on patients with heart disease,” says Udo Hoffmann, MD, MPH, director of the Cardiac MR PET CT program at Massachusetts General Hospital (MGH) and corresponding author of the NEJM article. “Although the use of CCTA added to the amount of diagnostic testing used in the evaluation process, compared with current standard protocols it significantly reduced length of stay without increasing costs.”

CCTA combines advanced CT scanning with the use of intravenous contrast material to produce detailed images of blood vessels supplying the heart without the need for cardiac catheterization. Several previous studies, including an immediate predecessor to the current one, have indicated that CCTA can effectively distinguish chest pain patients that do not have coronary artery disease, but those studies all had such limitations as lack of a control group or limited analysis of factors like costs and radiation exposure. The current study — ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography)-II — was designed to determine whether a CCTA-based evaluation strategy could improve clinical decision making at different hospitals across the country.

From April 2010 to January 2012, patients arriving at the participating hospitals’ EDs for evaluation of chest pain who had no history of cardiovascular disease and whose initial tests — ECG and measurement of the biomarker troponin — did not clearly indicate a heart attack were invited to participate in the trial. Those who agreed to participate were randomly assigned to one of two groups. The control group proceeded with standard evaluation, with all diagnostic and treatment decisions being made by hospital physicians not part of the study group. The other group had CCTA as part of their ED evaluation, with the results being shared with attending physicians who, again, made all clinical decisions. Participants who were discharged from the hospital within 24 hours of arrival were called within 72 hours to assess their status, and all participants were called 28 days after hospital discharge and asked whether any return ED visits or rehospitalizations had taken place. Participant responses were verified by checking their medical records. About 1,000 patients completed the study, including the 28-day followup.

The investigators found that participants in the CCTA group had significant reductions in the amount of time from ED arrival until discharge either from the ED or after a hospital stay, with half of the CCTA group being discharged within 8.6 hours but only 10 percent of the control group being released so quickly. The amount of time until a diagnosis of heart disease was either ruled out or confirmed was also shorter for the CCTA group than for the controls, and more patients receiving CCTA were discharged directly from the ED rather than being admitted to an observation unit. The percentage of patients actually diagnosed with heart disease was similar in both groups at around 8 percent, and there were no missed diagnoses in either group.

Analysis of total clinical resources used from arrival to discharge indicated that CCTA participants had more diagnostic procedures than control group members, but the difference was not statistically significant. Neither were there any significant differences between groups in total costs through the 28-day followup in those participants for whom cost information was available. CCTA group participants were exposed to higher cumulative doses of radiation, but the authors note that recent studies have indicated that CCTA can often be successfully performed using lower doses and suggest that future studies test the utility of low-dose CCTA examination.

“It’s very important to strive for the greatest efficiency in diagnostic testing, and in this study, additional testing was primarily carried out in patients found to have coronary artery disease,” Hoffmann says. “There also were fewer adverse clinical events in those receiving CCTA, although the study group was too small to conclude that CCTA reduced those risks.

“Showing at a variety of clinical sites that CCTA is at least as good as standard ED evaluation without increasing costs elevates the procedure from one appropriate only for specialized settings to one that can be applied in many centers,” he adds. “I’d really like to commend the commitment and teamwork of all the participating sites and departments, which was essential to the successful completion of this study.” Hoffmann is an associate professor of Radiology at Harvard Medical School.

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The above story is reprinted from materials provided by Massachusetts General Hospital.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Udo Hoffmann, Quynh A. Truong, David A. Schoenfeld, Eric T. Chou, Pamela K. Woodard, John T. Nagurney, J. Hector Pope, Thomas H. Hauser, Charles S. White, Scott G. Weiner, Shant Kalanjian, Michael E. Mullins, Issam Mikati, W. Frank Peacock, Pearl Zakroysky, Douglas Hayden, Alexander Goehler, Hang Lee, G. Scott Gazelle, Stephen D. Wiviott, Jerome L. Fleg, James E. Udelson. Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain. New England Journal of Medicine, 2012; 367 (4): 299 DOI: 10.1056/NEJMoa1201161

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Ancient Incan mummy had lung infection, according to novel proteomics analysis


ScienceDaily (July 25, 2012) — A 500-year-old frozen Incan mummy suffered from a bacterial lung infection at the time of its death, as revealed by a novel proteomics method that shows evidence of an active pathogenic infection in an ancient sample for the first time.

The full report is published July 25 in the open access journal PLoS ONE.

Detecting diseases in ancient remains is often fraught with difficulty, especially because of contamination. Techniques based on microbe DNA can easily be confused by environmental contamination, and they can only confirm that the pathogen was present, not that the person was infected, but the researchers behind the study, led by Angelique Corthals of the John Jay College of Criminal Justice, City University of New York, found a way around this problem. They used proteomics, focusing on protein rather than DNA remains, to profile immune system response from degraded samples taken from 500 year-old mummies.

The team swabbed the lips of two Andean Inca mummies, buried at 22,000-feet elevation and originally discovered in 1999, and compared the proteins they found to large databases of the human genome. They found that the protein profile from the mummy of a 15-year old girl, called “The Maiden,” was similar to that of chronic respiratory infection patients, and the analysis of the DNA showed the presence of probably pathogenic bacteria in the genus Mycobacterium, responsible for upper respiratory tract infections and tuberculosis. In addition, X-rays of the lungs of the Maiden showed signs of lung infection at the time of death. Proteomics, DNA, and x-rays from another mummy found together with the Maiden did not show signs of respiratory infection.

“Pathogen detection in ancient tissues isn’t new, but until now it’s been impossible to say whether the infectious agent was latent or active,” says Corthals. “Our technique opens a new door to solving some of history’s biggest mysteries, such as the reasons why the flu of 1918 was so devastating. It will also enhance our understanding of our future’s greatest threats, such as the emergence of new infectious agents or re-emergence of known infectious diseases.”

“Our study is the first of its kind since rather than looking for the pathogen, which is notoriously difficult to do in historical samples, we are looking at the immune system protein profile of the “patient,” which more accurately tells us that there was indeed an infection at the time of death.” or “Our study opens the door to solving many historical and current biomedical and forensic mysteries, from understanding why the plague of 1918 was so lethal, to finding out which pathogen is responsible for death in cases of multiple infections.”

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The above story is reprinted from materials provided by Public Library of Science.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Angelique Corthals, Antonius Koller, Dwight W. Martin, Robert Rieger, Emily I. Chen, Mario Bernaski, Gabriella Recagno, Liliana M. Dávalos. Detecting the Immune System Response of a 500 Year-Old Inca Mummy. PLoS ONE, 2012; 7 (7): e41244 DOI: 10.1371/journal.pone.0041244

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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