Postorthodontic root approximation after opening space for maxillary lateral incisor implants.

INTRODUCTION: Orthodontic space opening during adolescence is a common treatment for congenitally missing maxillary lateral incisors. Because of continued facial growth and compensatory tooth eruption, several years can elapse between completion of orthodontic treatment for a teenage patient and implant placement. There are reports that, after successful orthodontic opening of the implant space, the central incisor and canine roots reapproximate during retention and prevent implant placement. METHODS: To study this phenomenon, the records of 94 patients with missing maxillary lateral incisors were collected. Periapical and panoramic radiographs were used to measure intercoronal and interradicular distances between the central incisor and the canine adjacent to the missing lateral incisor before and after orthodontic treatment and at implant placement. RESULTS: Although root approximation between the adjacent central incisor and canine during retention did not occur consistently, 11% of the patients experienced relapse significant enough to prevent implant placement. CONCLUSIONS: To ensure sufficient space for implant placement, we recommend at least 6.3 mm of intercoronal space and 5.7 mm of interradicular space between the adjacent central incisor and canine. A bonded wire or resin-bonded bridge will help to reduce root approximation that might occur during retention.

HER-2 overexpression differentially alters transforming growth factor-beta responses in luminal versus mesenchymal human breast cancer cells.

INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-beta) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-beta1 on breast cancer cells in the presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays were used to determine the effect of TGF-beta on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-beta1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-beta signaling pathway was assessed using TGF-beta1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-beta1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-beta in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-beta induced pro-invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-beta. In contrast, HER-2 and TGF-beta signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model.