Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma

Copyright (c) 2010 Taylor & Francis. This is an electronic version of an article published in "GYNECOLOGICAL ENDOCRINOLOGY, Volume 26, Issue 3, pages 220-229 (2010)". GYNECOLOGICAL ENDOCRINOLOGY is available online at: https://doi.org/10.3109/09513590903215482Cyclin-dependent-kinase (cdk) inhibitor, p27<SUKip1</SU (p27), has been shown to participate in progestin-induced growth suppression of normal endometrial glands. To analyse the molecular mechanisms regulating p27 protein, we examined immunohistochemical expression of the SCF<SUSkp2</SU (Skp1-Cullin-F-box protein) complex factors, i.e. Skp1, Cul1 and Skp2, and compared them with that of p27, steroid receptors and Ki-67. In normal endometrial glands, the expression of Skp2 was observed in the proliferative phase, whereas that of p27 was observed in the secretory phase. Cultured normal endometrial glandular cells showed that progesterone induced the down-regulation of Skp2 along with up-regulation of p27. In endometrial carcinomas, the inverse topological correlation between Skp2 and p27 was evident in 39/66 (59%) cases, and the expression of Skp2 showed a strong correlation with Ki-67. These findings suggest that the expression of SCF<SUSkp2</SU complex changes during the menstrual cycle in normal endometrium and the SCF<SUSkp2</SU ubiquitin-proteasome pathway may also work in endometrial carcinomas.</.ArticleGYNECOLOGICAL ENDOCRINOLOGY. 26(3):220-229 (2010)journal articl

Methylation of MGMT and ADAMTS14 in normal colon mucosa : biomarkers of a field defect for cancerization preferentially targeting elder African-Americans

Altres ajuts: National Institutes of Health Grant R37CA63585, RO1CA83017 i RO1CA157328Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North Americ

Validation of Addenbrooke's cognitive examination III for detecting mild cognitive impairment and dementia in Japan

BACKGROUND:Early detection of mild cognitive impairment (MCI) and dementia is very important to begin appropriate treatment promptly and to prevent disease exacerbation. We investigated the screening accuracy of the Japanese version of Addenbrooke's Cognitive Examination III (ACE-III) to diagnose MCI and dementia. METHODS:The original ACE-III was translated and adapted to Japanese. It was then administered to a Japanese population. The Hasegawa Dementia Scale-revised (HDS-R) and Mini-mental State Examination (MMSE) were also applied to evaluate cognitive dysfunction. In total, 389 subjects (dementia = 178, MCI = 137, controls = 73) took part in our study. RESULTS:The optimal ACE-III cut-off scores to detect MCI and dementia were 88/89 (sensitivity 0.77, specificity 0.92) and 75/76 (sensitivity 0.82, specificity 0.90), respectively. ACE-III was superior to HDS-R and MMSE in the detection of MCI or dementia. The internal consistency, test-retest reliability, and inter-rater reliability of ACE-III were excellent. CONCLUSIONS:ACE-III is a useful cognitive test to detect MCI and dementia. ACE-III may be widely useful in clinical practice

ガクガンメン リョウイキ ニオケル コツチユ ニ タイスル テイシュツリョク チョウオンパ パルス ショウシャ ノ シヨウ ケイケン

Fracture healing has traditionally been thought to be a naturally optimized process with predetermined time-course for bone metabolism, and no one had had an idea that fracture healing may be manipulated to occur at a faster rate. In 1980s, the use of low-intensity pulsed ultrasound (LIPUS) was demonstrated with a significant promotion of bone healing and LIPUS has been used extensively for bone fractures in the limbs. On the other hand, the effectiveness of LIPUS for maxillofacial bone fractures has not been studied yet. In clinical orthodontics, there are many cases closely related to bone healing: the traumatic bone fracture in maxillofacial region, the osteotomy of jaw deformity, and the bone grafting in to alveolar cleft. The purpose of this study was to examine the benefit of LIPUS to the acceleration of maxillofacial bone healing. Thirty-five patients received LIPUS after surgery served as subjects. Of total subjects, 11 patients had surgery for maxillofacial bone fracture fixation, 7 patients with jaw deformity had orthognathic surgery, and 17 patients affected by cleft lip and palate underwent alveolar cleft bone grafting. Five-seven days after surgery, the patient received 15 minutes of LIPUS (BR sonic-pro, ITO Co., Tokyo, Japan) per day for 14 days. A LIPUS signal was transmitted at a frequency of 1.0 MHz with a spatial-average intensity of 160 mW and pulsed 1: 4. In addition, we used the visual analogue scale (VAS) for pain assessment, and simple radiographs and computed tomography (CT) for evaluation of the bone healing. In most cases, pain disappeared within one week after surgery. In the patients with bone fracture fixation or jaw osteotomy, bone healing was validated by plain radiographs and/or CT taken at 3 months after surgery, leading to stable occlusion. In the cases with alveolar bone grafting, early bone formation was observed from CT taken at 3 months after surgery. In addition, the catabolic effects of LIPUS exposure were not found at all. In conclusion, LIPUS application might involve in acceleration of maxillofacial bone healing after surgery. Therefore, LIPUS may be a promising therapeutic tool for bone healing in maxillofacial region

A novel 10Be proxy of cosmic-ray intensity between 11-28 ka from Dome Fuji, Antarctica.

第2回極域科学シンポジウム　氷床コアセッション 11月16日（水） 国立極地研究所 2階大会議室前フロ

Cosmogenic beryllium 10 in ice cores and cosmic-ray stratigraphy

第2回極域科学シンポジウム　氷床コアセッション 11月16日（水） 国立極地研究所 2階大会議

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset