Comparison and precision of visceral adipose tissue measurement techniques in a multisite longitudinal study using MRI.

BACKGROUND: Measurement of visceral adipose tissue (VAT) using magnetic resonance imaging (MRI) is considered accurate and safe. Single slice measurements perform similar to volumetric measurements for cross-sectional observation studies but may not perform as well for longitudinal studies. This study compared the performance of single slice to volumetric VAT measurements in a prospective longitudinal study. Consistency of results across sites and over time was also evaluated. METHODS: A total of 935 healthy participants were recruited and scanned with MRI twice, approximately six months apart as part of a randomized, controlled, parallel arm, unblinded study conducted at four clinical centers in the United States. A 3D Dixon MRI sequence was used to image the abdomen, and visceral fat volumes were quantified for the abdomen, reduced coverage volumes (11 and 25 slices), and at single slices positioned at anatomical landmarks. A traveling phantom was scanned twice at all imaging sites. RESULTS: The correlation of single slice VAT measurement to full abdomen volumetric measurements ranged from 0.78 to 0.93 for cross-sectional observation measurements and 0.30 to 0.55 for longitudinal change. Reduced coverage volumetric measurement outperformed single slice measurements but still showed improved precision with more slices with cross-sectional observation and longitudinal correlations of 0.94 and 0.66 for 11 slices and 0.94 and 0.70 for 25 slices, respectively. No significant differences were observed across sites or over time with the traveling phantom and the volume measurements had a standard deviation of 14.1 mL, 2.6% of the measured volume. CONCLUSION: Single slice VAT measurements had significantly lower correlation with abdomen VAT volume for longitudinal change than for cross-sectional observation measurements and may not be suitable for longitudinal studies. Data from multiple sites, different scanners, and over time did not show significant differences.

Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of young pediatric patients with medulloblastoma.

PURPOSE: To investigate the long-term effects of vertebral-body-sparing proton craniospinal irradiation (CSI) on the spine of young patients with medulloblastoma. METHODS AND MATERIALS: Six children between the ages of 3 and 5 years with medulloblastoma were treated with vertebral-body-sparing proton CSI after maximal safe resection. Radiation therapy was delivered in the supine position with posterior beams targeting the craniospinal axis, and the proton beam was stopped anterior to the thecal sac. Patients were treated with a dose of either 23.4 Gy or 36 Gy to the craniospinal axis followed by a boost to the posterior fossa and any metastatic lesions. Chemotherapy varied by protocol. Radiographic effects on the spine were evaluated with serial imaging, either with magnetic resonance imaging scans or plain film using Cobb angle calculations, the presence of thoracic lordosis, lumbar vertebral body-to-disc height ratios, and anterior-posterior height ratios. Clinical outcomes were evaluated by patient/family interview and medical chart review. RESULTS: Overall survival and disease free survival were 83% (5/6) at follow-up. Median clinical and radiographic follow-up were 13.6 years and 12.3 years, respectively. Two patients were clinically diagnosed with scoliosis and treated conservatively. At the time of follow-up, no patients had experienced chronic back pain or required spine surgery. No patients were identified to have thoracic lordosis. Diminished growth of the posterior portions of vertebral bodies was identified in all patients, with an average posterior to anterior ratio of 0.88, which was accompanied by compensatory hypertrophy of the posterior intervertebral discs. CONCLUSION: Vertebral-body-sparing CSI with proton beam did not appear to cause increased severe spinal abnormalities in patients treated at our institution. This approach could be considered in future clinical trials in an effort to reduce toxicity and the risk of secondary malignancy and to improve adult height.

Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.

BACKGROUND: The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. METHODS: Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. RESULTS: In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. CONCLUSION: Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.