Endometrial Cancer and Hypermethylation: Regulation of DNA and MicroRNA by Epigenetics

Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies

Maxillary stability after le Fort i osteotomy using three different plate systems

The purpose of this study was to compare postoperative changes in maxillary stability after Le Fort I osteotomy in three groups: with an unsintered hydroxyapatite (u-HA)/poly-l-lactic acid (PLLA) plate; a PLLA plate; and a titanium plate. Subjects comprised 60 Japanese patients diagnosed with mandibular prognathism. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy. All patients were randomized in groups of 20 to a u-HA/PLLA group, a PLLA plate group and a titanium plate group. Changes in postoperative time intervals between the plate groups were compared using lateral and posteroanterior cephalography. The uHA/PLLA group had significantly larger values than the PLLA group regarding change of mx1-S perpendicular to SN between 3 and 12 months (T3) (P = 0.0269). The uHA/PLLA group had a significantly larger value than the PLLA group regarding change of S-A perpendicular to SN between baseline and 1 month (T1) (P = 0.0257). There was no significant difference in the other measurements. This study suggests that maxillary stability with satisfactory results could be obtained in the u-HA/PLLA, PLLA plate and titanium plate groups, although there was a slight difference between the u-HA/PLLA and PLLA plate systems in Le Fort I osteotomy. © 2012 International Association of Oral and Maxillofacial Surgeons

Failure of DNA double-strand break repair by tau mediates Alzheimer’s disease pathology in vitro

DNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer’s disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy

Changes in temporomandibular joint and ramus after sagittal split ramus osteotomy in mandibular prognathism patients with and without asymmetry

The purpose of this study was to examine the changes in the temporomandibular joint (TMJ) and ramus after sagittal split ramus osteotomy (SSRO) with and without Le Fort I osteotomy. The subjects consisted of 87 Japanese patients diagnosed with mandibular prognathism with and without asymmetry. They were divided into 2 groups (42 symmetric patients and 45 asymmetric patients). The TMJ disc tissue was assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar and ramus angle were assessed by computed tomography (CT) preoperatively and postoperatively. Medial joint space on the deviation side in the asymmetry group was significantly larger than that in the symmetry group (P = 0.0043), and coronal ramus angle on the non-deviation side in the asymmetry group was significantly larger than that in the symmetry group preoperatively (P = 0.0240). The horizontal condylar angle on the deviation side in the asymmetry group was significantly larger than that in the symmetry group (P = 0.0302), posterior joint space on the non-deviation side in the symmetry group was significantly larger than that in the asymmetry group postoperatively (P = 0.00391). The postoperative anterior joint space was significantly larger than the preoperative value on both sides in both groups (the deviation side in the symmetry group: P = 0.0016, the non-deviation side in the symmetry group: P < 0.0001, the deviation side in the asymmetry group: P = 0.0040, the non-deviation side in the asymmetry group: P = 0.0024). The preoperative disc position could was not changed in either group. These results suggest that significant expansion of anterior joint space could occur on the deviation side and non-deviation side in the asymmetry group as well as on both sides in the symmetry group, although disc position did not change in either group. © 2011 European Association for Cranio-Maxillo-Facial Surgery

Relationship between DNA Mismatch Repair Deficiency and Endometrial Cancer

Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Lynch syndrome is thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene. An aberration in the MMR gene prevents accurate repair of base mismatches produced during DNA replication. This phenomenon can lead to an increased frequency of errors in target genes involved in carcinogenesis, resulting in cancerization of the cell. On the other hand, aberrant DNA methylation is thought to play a key role in sporadic endometrial carcinogenesis. Hypermethylation of unmethylated CpG islands in the promoter regions of cancer-related genes associated with DNA repair leads to the cell becoming cancerous. Thus, both genetic and epigenetic changes are intricately involved in the process through which cells become cancerous. In this review, we introduce the latest findings on the DNA mismatch repair pathway in endometrial cancer

A hypothesis on the desired postoperative position of the condyle in orthognathic surgery: a review

It is very important to clarify the relationship between a dentofacial structure and a temporomandibular joint (TMJ) structure in orthognathic surgery. Recently, it was reported that the skeletal and occlusal patterns were associated with the TMJ morphology, including the disk position. In orthognathic surgery, some surgeons state that alterations in the condylar position from surgery can lead to malocclusion associated with the risk of early relapse, and also favor the development of temporomandibular disorders. For these reasons, several positioning devices have been proposed and applied, but now there is no scientific evidence to support the use of condylar positioning devices. There are some reasons why scientific evidence cannot be obtained; however, it also includes the question of whether the preoperative position of the condyle is the desired postoperative position. The purpose of this study was to verify the desired condylar position in orthognathic surgery, based on literature on the postoperative condylar position in orthognathic surgery. From the studies reviewed, it was suggested that the preoperative position of the condyle was not the desired postoperative position in orthognathic surgery. © 2012 Elsevier Inc. All rights reserved