August 2006
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Research
Gene activity patterns may help classify tumors
Biologists have long speculated that cancer growth and embryonic development share common features. Hongye Liu, PhD, and colleagues in the Children's Hospital Informatics Program (CHIP) now provide proof, showing that lung tumors and embryonic lungs have similar patterns of gene expression, turning many of the same genes' activity "up" or "down." Gene expression profiles also predicted cancer prognosis, sometimes better than existing methods.
The researchers compared gene activity in lung tumors from 186 patients with activity during normal embryonic lung development in mice. About 600 genes had altered activity in both situations; of these, about 30 belong to known or suspected biological pathways in cancer, and several offer promising targets for drugs.
Liu and colleagues could also predict cancer survival, using lung development as a framework. Tumors whose gene expression profile most resembled expression during early lung development had the worst prognosis, while tumors with a profile like that in late-stage lung development had the best prognosis. Even within a single subtype, stage I adenocarcinoma, survival times varied according to gene expression patterns.
Currently, lung cancer is commonly misclassified, delaying proper treatment. Carcinoid and small-cell lung cancers, for example, have very different prognoses and optimal treatments, but are often mistaken for each other in biopsy specimens. "By employing molecular profiling, we can distinguish these two cancers," Liu says.
The study was published online in PLoS Medicine on July 4. Co-authors included CHIP director Isaac Kohane, MD, PhD, and Alvin Kho, PhD.
Why is academic testing leaving children behind?
Low-income children tend to do poorly on high-stakes achievement tests like the Massachusetts Comprehensive Assessment System (MCAS). A pilot study led by Deborah Waber, PhD, in Children's Hospital Boston's Department of Psychiatry, suggests their low scores may arise from developmental issues—particularly in "executive" functions like organization, planning and control over thoughts and actions. Poverty-related factors like poor nutrition, exposure to violence or toxic agents and disorganized or stressful environments can disrupt children's developing nervous systems, Waber says.
Using cognitive testing and teacher questionnaires, the study evaluated 91 fifth-graders from two low-income Boston schools served by the Children's Hospital Neighborhood Partnership (school-based mental health services). Overall, the children's executive functions were poorer than average, and more than half had "failing" or "needs improvement" scores on the fourth-grade MCAS English and math tests. Executive function correlated closely with MCAS performance: Tests of mental processing speed and short-term memory, combined with teacher ratings on items like finishing assignments, checking work for mistakes and organization of desk and backpack, accurately predicted whether a child would pass or fail the MCAS 86 percent of the time.
Waber now hopes to expand her study, published in Developmental Neuropsychology. She believes that funds used for testing would be better spent on early diagnostic assessment and helping children develop executive functions, through measures like smaller classrooms in the younger grades, explicit teaching of organizational skills and adoption of special-education techniques.
Children living with smokers have more complications in the OR
Children's Hospital Boston researchers have identified another problem related to secondhand smoke: a greater risk for respiratory complications during outpatient surgical procedures.
Dwight Jones, MD, in Children's Department of Otolaryngology, and his Brigham and Women's Hospital colleague Neil Bhattacharyya, MD, followed 405 pediatric surgical patients, including 168 from households with smokers. The children's procedures ranged from drainage of middle-ear fluid to circumcision to hernia repair. All received general anesthesia and oxygen through a face mask.
Children living with smokers had significantly more airway complications in the operating room—excessive mucus secretion, constriction of the larynx or bronchial tubes and actual airway obstruction. The more cigarettes smoked per day in the home, the more severe the complications. Some children needed bronchodilators and extra oxygen, and some were admitted overnight. Complications were also increased in the recovery room.
"It was during wakeup in the operating room that they did the worst," says Jones. "We had a harder time because of choking, gagging and secretions while the children were coming out of anesthesia."
The findings, published in the July 1 issue of Otolaryngology-Head and Neck Surgery, suggest that children who live with smokers may need more attention to their airways during surgery, especially when receiving face-mask ventilation.
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