Survivin is a novel target of CD44-promoted breast tumor invasion.

The hyaluronan (HA) receptor CD44 plays an essential role in cell-cell or cell-extracellular matrix communications and is a bioactive signal transmitter. Although a number of studies have described the function of CD44 in breast cancer (BC) metastasis, the underlying mechanisms have yet to be determined. By using a validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell line combined with microarray analysis, we identified survivin (SVV) as a potential downstream transcriptional target of CD44. To test the hypothesis that SVV underpins CD44-promoted BC cell invasion, we combined molecular and pharmacologic approaches and showed that CD44 induction increased SVV expression levels, which in turn promotes BC cell invasion. Further, clinical analysis of breast tissue samples showed that SVV expression patterns paralleled those of the standard form of CD44 during breast tumor progression. More interestingly, we identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44 activation and SVV transcription. In addition to identifying SVV as a target for HA/CD44 signaling, this investigation provides a better understanding of the molecular mechanisms that underpin the novel function of SVV in breast cancer metastasis.

Medulloblastoma variants and survival at a children's hospital.

Our 25 year experience with 35 medulloblastomas included classic (NOS) 22 (63%), anaplastic (ANA) 5(14%), desmoplastic (DES) 4(11%), excessive nodularity (EN) 3(9%), and large cell (LC) 1(3%). Overall 5, 10, and 15 year survivals were .6631, .5851, and .5051. Those under 3 years at diagnosis had an overall 2 year survival of .4379. Two survived 17(NOS) and 19 (EN) years. In the 26 children 3 years or older, late deaths occurred at 8, 8, and 14 years (5, 10, 15 year survivals .7375, .6392, .5114). Because late deaths occur; continued follow-up of these children is required.

Inchoate CD8+ T cell responses in neonatal mice permit influenza-induced persistent pulmonary dysfunction.

Influenza infection remains a significant cause of pulmonary morbidity and mortality worldwide, with the highest hospitalization and mortality rates occurring in infants and elder adults. The mechanisms inducing this considerable morbidity and mortality are largely unknown. To address this question, we established a neonatal mouse model of influenza infection to test the hypothesis that the immaturity of the neonatal immune system is responsible for the severe pulmonary disease observed in infants. Seven-day-old mice were infected with influenza A virus (H1N1) and allowed to mature. As adults, these mice showed enhanced airway hyperreactivity, chronic pulmonary inflammation, and diffuse emphysematous-type lesions in the lungs. The adaptive immune responses of the neonates were much weaker than those of adults. This insufficiency appeared to be in both magnitude and functionality and was most apparent in the CD8(+) T cell population. To determine the role of neonatal CD8(+) T cells in disease outcome, adult, naive CD8(+) T cells were adoptively transferred into neonates before infection. Neonatal mice receiving the adult CD8(+) T cells had significantly lower pulmonary viral titers and greatly improved pulmonary function as adults (airway resistance similar to SHAM). Additional adoptive transfer studies using adult CD8(+) T cells from IFN-gamma-deficient mice demonstrated the importance of IFN-gamma from CD8(+) T cells in controlling the infection and in determining disease outcome. Our data indicate that neonates are more vulnerable to severe infections due to immaturity of their immune system and emphasize the importance of vaccination in infants.

Hypertrophic cervical elongation: clinical and histological correlations.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to define the diagnosis of hypertrophic cervical elongation clinically and to perform histochemical and histological evaluations of patients with and without hypertrophic cervical elongation. METHODS: This prospective study was conducted at Louisiana State University between December 2005 and May 2008. Fourteen women with cervical elongation and 28 women without prolapse were studied. RESULTS: The amounts of elastin, collagen, and smooth muscle did not differ between study and control groups. Estrogen and progesterone receptor content in cervical elongation were elevated compared to the cervix of women without prolapse. Hypertrophic cervical elongation was defined as the difference between point C and point D of the Pelvic Organ Prolapse Quantification system greater than 8 cm. CONCLUSIONS: Estrogen and progesterone receptor levels are greater in women with hypertrophic cervical elongation compared with a normal cervix.