Estrogen induces genomic instability in high-risk HPV-infected cervix and promotes the carcinogenesis of cervical adenocarcinoma.

High-risk human papillomavirus (HPV) infection is the major cause of cervical cancer. However, the factors that modulate the process from infection to carcinogenesis are poorly understood. Although cervical cancer is clinically considered an estrogen-independent tumor, the role of estrogen in cervical cancer, particularly cervical adenocarcinoma, remains controversial. In this study, we showed that estrogen/GPR30 signaling induced genomic instability, which leads to carcinogenesis in high-risk HPV-infected endocervical columnar cell lines. The expression of estrogen receptors in a normal cervix was confirmed through immunohistochemical analysis which showed that G protein-coupled receptor 30 (GPR30) was predominantly expressed in endocervical glands and estrogen receptor-α (ERα) was expressed at higher levels in the squamous epithelium than in the cervical gland. E2 increased the proliferation of cervical cell lines, particularly normal endocervical columnar and adenocarcinoma cells via GPR30 rather than ERα, and increased the accumulation of DNA double-strand breaks (DSBs) in high-risk HPV-E6-expressing cells. The increase in DSBs was caused by the impairment of Rad 51 and accumulation of topoisomerase-2-DNA complexes under HPV-E6 expression. In addition, chromosomal aberrations increased in cells with E2-induced DSB accumulation. Collectively, we conclude that E2 exposure in high-risk HPV-infected cervical cells increases DSBs, leading to genomic instability and thus carcinogenesis via GPR30.

Horizontal alveolar ridge distraction osteogenesis in dogs: radiographic and histologic studies.

PURPOSE: This study was designed to evaluate the healing process in horizontal alveolar ridge distraction of the narrow alveolus in dogs. MATERIALS AND METHODS: Six beagle dogs weighing approximately 9 to 10 kg were used in this experiment. Horizontal alveolar ridge distraction was performed in the right mandible, where the premolars had been extracted 12 weeks previously. Twelve days after the completion of distraction, the lengthening apparatus was removed. The distracted site was evaluated at 12 and 24 weeks after the removal. RESULTS: At 12 weeks, thin woven bone was observed at the distracted site growing from the surface of the original lingual cortical bone toward the transport segment. At 24 weeks, the distracted site had fully changed into new mature lamellar bone, but the transport segments had been almost completely resorbed. DISCUSSION: Horizontal alveolar ridge distraction was performed successfully in beagle dogs even though the apparatus was removed 12 days after the completion of distraction. The most important feature of this technique is the resorption of the transport segment. CONCLUSION: Horizontal alveolar ridge distraction can be a beneficial technique for augmenting the alveolar ridge horizontally in the buccolingually reduced alveolar process before the placement of implants.

Endosseous implants in horizontal alveolar ridge distraction osteogenesis.

PURPOSE: This study evaluated horizontal distraction of the narrow alveolar ridge in dogs and the possibility of achieving osseointegration of implants placed into the distracted site during a consolidation period. MATERIALS AND METHODS: Six beagle dogs weighing approximately 9 to 10 kg were used in this experiment. Twelve weeks after extraction of the mandibular premolars, horizontal alveolar ridge distraction was performed using an originally designed lengthening apparatus. Twelve days after the completion of distraction, screw-type implants were placed into the distracted site. RESULTS: Twelve weeks after the placement of implants, thin lamellar bone rose horizontally from the transport segment toward the surface of the implant. Twenty-four weeks after their placement, the implants were fully embedded in mature lamellar bone, and direct bone contact with the implant surface could be seen. DISCUSSION: Horizontal alveolar ridge distraction was performed successfully by using a lengthening apparatus in the narrow alveolar models. Osseointegration was achieved even though the implants were placed into the distracted site during the consolidation period. CONCLUSION: Horizontal alveolar ridge distraction can be a beneficial technique in the placement of implants In the narrow alveolar ridge in the dog population.