Genetic defects in the Wnt-1 signaling pathway contribute to human tumor progression and are especially prevalent in colorectal cancer. We screened mouse C57MG cells to isolate mRNAs induced by Wnt-1 and identified Stra6, an mRNA known to be up-regulated by retinoic acid. Up-regulation of Stra6 mRNA was also observed in hyperplastic mammary tissue and mammary gland tumors from transgenic mice expressing Wnt-1 and in human tumors that frequently harbor defects in Wnt-1 signaling. Stimulation of C57MG cells with retinoic acid plus Wnt-1 resulted in expression of Stra6 transcript to levels greatly exceeding that observed with either stimulus alone. This synergy could be explained in part by the up-regulation of retinoic acid receptor-gamma that was observed in response to Wnt-1 signaling. Accordingly, treatment of human colorectal cancer cell lines with retinoic acid resulted in the up-regulation of Stra6 mRNA and accumulation of Stra6 protein at the cell membrane. The data support a model in which Wnt-1 signaling synergizes with retinoids to activate retinoic acid receptor-gamma-responsive genes in human cancers.

OBJECTIVE:To analyze the morphology of the maxillary crest in infants with Pierre Robin sequence using an anthropometric coordinate system and to compare the data with those of healthy infants.SETTING:The study was performed at a craniofacial center servicing a large geographic area.PARTICIPANTS:The study involved eight infants aged 1-28 days (average, 7 days) with an established diagnosis of Pierre Robin sequence and six healthy infants aged 1-43 days (average, 22 days).MAIN OUTCOME MEASURES:Physical models of the maxilla and face obtained by alginate replication were analyzed by computer morphometry yielding the three-dimensional topology of the maxillary crest.RESULTS:The maxillary crest of children with Pierre Robin sequence shows an increased inclination relative to the transverse plane (30 +/- 3.9 degrees) as compared with that of healthy infants (20 +/- 2.9 degrees). The maxillary crest of the patients is shortened in the sagittal direction by comparison with healthy controls.CONCLUSIONS:The increased inclination of the maxilla in infants with Pierre Robin sequence may aggravate the retroposition of the mandible and may thus be a pathogenetic factor contributing to the severe respiratory problems.

OBJECTIVE:To describe a method of determining the three-dimensional topology of the palatal crest relative to a reproducible anthropomorphic coordinate system in newborn infants with unilateral cleft palate. For this purpose, physical models of the maxilla and face were analyzed by computer morphometry.DESIGN:The study was limited to infants referred to the craniofacial center during the first 11 days after birth.SETTING:The study was performed at a craniofacial center servicing a large geographic area.PARTICIPANTS:The method was applied to 12 infants with unilateral cleft lip, alveolus, and palate (eight patients with left-side clefts and four with right-side clefts).MAIN OUTCOME MEASURES:The three-dimensional topology of the palatal crest referenced to an anthropometric coordinate system was the primary outcome measure. The anthropometric reference system is defined by the tragus points and the midpoint of a line connecting the endocanthia.RESULTS:The topology of the maxillary crests of the patients was characterized by considerable variability. The center of the premaxilla as defined by the attachment of the frenulum was frequently displaced by several millimeters from the midsagittal plane. The displacement was to the left in infants with right-side clefts and to the right in infants with left-side clefts. The premaxilla can be rotated by more than 30 degrees relative to the normal position. No significant retroposition of the minor segment as determined by the location of the tuber points was found. Several morphometric anomalies were found to be correlated linearly.CONCLUSIONS:We propose that the morphologic deviations are in part caused by the neuromotor activity of the tongue and of the interrupted M. orbicularis oris. The data can serve as the starting point for a longitudinal study of craniofacial development in children with cleft palate and for studies on the efficacy of different therapeutic approaches.