Posts Tagged Personalized Medicine

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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MRSA cases in academic hospitals double in five years


ScienceDaily (July 26, 2012) — Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) doubled at academic medical centers in the U.S. between 2003 and 2008, according to a report published in the August issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

Researchers from the University of Chicago Medicine and the University HealthSystem Consortium (UHC) estimate hospitalizations increased from about 21 out of every 1,000 patients hospitalized in 2003 to about 42 out of every 1,000 in 2008, or almost 1 in 20 inpatients. “The rapid increase means that the number of people hospitalized with recorded MRSA infections exceeded the number hospitalized with AIDS and influenza combined in each of the last three years of the survey: 2006, 2007, and 2008,” said Michael David, MD, PhD, an assistant professor of medicine at the University of Chicago and one of the study’s authors.

The findings run counter to a recent CDC study that found MRSA cases in hospitals were declining. The CDC study looked only at cases of invasive MRSA — infections found in the blood, spinal fluid, or deep tissue. It excluded infections of the skin, which the UHC study includes.

MRSA infections, which cannot be treated with antibiotics related to penicillin, have become common since the late 1990s. These infections can affect any part of the body, including the skin, blood stream, joints, bones, and lungs.

The researchers attribute much of the overall increase they detected to community-associated infections — those that were contracted outside the healthcare setting. When MRSA first emerged it was primarily contracted in hospitals or nursing homes. “Community-associated MRSA infections, first described in 1998, have increased in prevalence greatly in the U.S. in the last decade,” David said. “Meanwhile, healthcare-associated strains have generally been declining.”

The study utilized the UHC database, which includes data from 90 percent of all not-for-profit academic medical centers in the U.S. However, like many such databases, the UHC data are based on billing codes hospitals submit to insurance companies, which often underestimate MRSA cases. For example, hospitals might not report MRSA cases that do not affect insurance reimbursement for that particular patient. In other cases, hospitals might be limited in the number of billing codes they can submit for each patient, which can result in a MRSA code being left off the billing report if it was not among the primary diagnoses.

David and his team corrected for these errors by using detailed patient observations from the University of Chicago Medical Center and three other hospitals. They looked at patient records to find the actual number of MRSA cases in each hospital over a three-year period. The team then checked the insurance billing data to see how many of those cases were actually recorded. They found that the billing data missed one-third to one-half of actual MRSA cases at the four hospitals. They used that rate of error as a proxy to correct the billing data from other 420 hospitals in the UHC database and arrive at the final estimates.

“I think this is still an underestimate of actual cases,” David said. “But we can say with some assurance that this correction gives us a more accurate lower bound for how many cases [of MRSA] there actually are. What’s clear from our data is that cases were on the rise in academic hospitals in 2003 to 2008.”

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The above story is reprinted from materials provided by University of Chicago Press Journals, 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. Michael Z. David, Sofia Medvedev, Samuel F. Hohmann, Bernard Ewigman, Robert S. Daum. Increasing Burden of Methicillin-Resistant Staphylococcus aureus Hospitalizations at US Academic Medical Centers, 2003? Infection Control and Hospital Epidemiology, August 2012 [link]

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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