Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.
Jung, Hyun Ji;Kim, Hye Jin;Kwon, Oran;Lee, Won Jun
Journal of Life Science
/
v.25
no.11
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pp.1214-1222
/
2015
The purpose of this study was to determine the effect of Pueraria lobate-root based combination supplementation containing Rehmannia glutinosa and exercise on histone modification in ovariectomized rat hindlimb skeletal muscle. Sixty rats were fed with high fat diet and randomly assigned into the following groups for 8 weeks: 1)HSV; High fat+Sedentary+Vehicle, 2)HSP; High fat+Sedentary+PR, 3)HSH; High fat+Sedentary+Estradiol, 4)HEV; High fat+Ex+Vehicle, 5)HEP; High fat+Ex+PR, 6)HEH; High fat+Ex+Estradiol. Exercise consisted of low intensity treadmill exercise(1-4th wk:15 m/min for 30 min, 5-8th wk: 18 m/min for 40 min, 5 times/week). The result of this study showed that exercise and Pueraria and Rehmannia glutinosa intake suppressed weight gain. Furthermore, exercise and Pueraria and Rehmannia glutinosa intake increased muscle mass. This study observed H3K9 acetylation and demethylation in plantaris muscle in exercised group, but no difference in soleus muscle. To test whether the decrease in HDAC4, HDAC5 and G9a mRNA levels after exercise and Pueraria/Rehmannia glutinosa intake, HDAC4, HDAC5 and G9a mRNA levels were determined by real-time PCR. Only exercise induced HDAC5 and G9a mRNA reduction in plantaris muscle, but not in soleus muscle. In conclusion, these data demonstrates that exercise and Pueraria/Rehmannia glutinosa intake effect on body compositions. These changes are regulated by epigenetic modifications, such as histone acetylation and methylation. Future studies should focus on gene-specific epigenetics and other epigenetic mechanism for Pueraria/Rehmannia glutinosa intake.
This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.
Kim, Yong-Dae;Suh, Bo-Su;Cho, Gil-Sung;Song, Si-Youn;Yoon, Seok-Keun;Song, Kei-Won
Journal of Yeungnam Medical Science
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v.18
no.2
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pp.199-207
/
2001
Background: Septoplasty with turbinate surgery is common surgical treatment in patients with septal deviation and chronic hypertrophic rhinitis. The aim of this study was to evaluation objective outcomes of septoplasty with turbinate surgery by analysis of subjective symptom score with objective acoustic rhinometric test before and after surgery, prospectively. Materials and Methods: We reviewed 45 adult patients which were done septoplasty with bilateral turbinectomy or turbinoplasty and followed up at least 3 months by one rhinologist from November 1999 to April 2000, prospectively. We analyzed subjective symptom score, minimal cross-sectional area (MCA), C-notch cross-sectional area, and total volume of both nasal cavity before and after surgery. Correlation test was studied between symptom improvement and acoustic rhinometric results. Results: Twenty nine cases were male and sixteen cases female. The average age was 26.9 year-old (range: 17 to 57 years). There was significantly improvement of symptom score in postoperative 3 months (p<0.05). There was significantly increased C-notch cross-sectional area and total volume in postoperative 3 months. Symptoms improvement were associated with acoustic rhinometric profiles, but, there was not significantly correlation. Conclusion: Septoplasty with turbinate surgery is considered to be effective for nasal obstruction in patients with septal deviation and turbinate hypertrophy. Acoustic rhinometric test is favorable objective test for evaluation of symptom improvement after septal surgery.
Infantile hypertrophic pyloric stensosis(IHPS) occurs in three of 1000 live births, and is a major cause of nonbilious vomiting of early infancy. It's etiology and pathogenesis however are still obscure. The operation of pyloromyotomy described by Ramstedt in 1912 remains the standard treatment. From January 1990 to July 1997, 64 infants with IHPS were treated at the Department of Pediatric Sursery, Yeungnam University Hospital. The ratio of male to female was 7:1, and the most prevalent age ranged from 2 weeks to 8 weeks(81.2 %) of age. Fifty-seven infants were first born (57.8 percent). The body weight of all patients at admission was below the 50 percentile. Age of onset of symptoms was between 2 and 4weeks of age in 23 cases(35.9 %). All infants had a history of nonbilious vomting, generally projectile in nature. Hypokalemia was noted in 14 cases(21.9 %) and hypochloremia in 26 cases(40.6 %). In the preoperative ultrasonography, the average muscle thickness, diameter, and length of the pylorus were 6.3 mm, 12.3 mm, and 17.8 mm. A total of 13 associated anomalies were noted in 12 patients. All cases were treated with Fredet-Ramstedt pyloromyotomy. Postoperative wound infection occured in 3 cases. Thirteen cases(20.3 %) presented intermittent nonprojectile vomiting after operation. With control of oral intake vomiting subsided within one week in 63 patients, and in thirteen days in another.
Infantile hypertrophic pyloric stenosis(IHPS), which occurs three of 1,000 live births, is a major cause of nonbilious vomiting of early infancy but its etiology and pathogenesis are still obscure. The operation of pyloromyotomy as described by Ramstedt in 1912 remains the standard of care for the treatment of IHPS. From January 1993 to October 1996, 35 infants with IHPS were surgically treated and the following results were obtained. 1. Thirty-five patients comprised 32 males and 3 females, and the ratio of male to female was 10.7:1. 2. The most prevalent age group was between 2 weeks and 8 weeks. 3. Of 35 infants, first born babies were 23 cases(65.7%). 4. Breast feeding was in 23 cases(65.7%). 5. The body weight percentile at admission was lower than 50 percentile in all 35 cases. 6. Onset of symptoms was predominantly between 1week and 2 weeks in 11 cases(31.4%). 7. All had a history of nonbilious vomting, generally projectile in nature. 8. In the measured serum electrolytes, hypokalemia was noted in 9 cases(25.7%), hypochloremia was observed in 14 cases(40.0%). 9. In the preoperative ultrasonography, the average muscle thickness, diameter, and length of the pylorus were 6.2mm, 12.1mm, and 17.9mm, respectively. 10. Among 35 cases, significant sonographic criteria of IHPS, muscle thickness of 5mm or more, were noted in 26 cases(83.9%). 11. A total of seven associated anomalies were noted in six patients. 12. All 35 cases were treated with Fredet-Ramstedt pyloromyotomy. 13. There were postoperative complications of wound infection in 2 cases. Intermittent nonprojectile vomiting was presented in 8 cases(22.9%) after operation, but one of them was relieved in 13 days and the rest were relieved within one week by adjustment of oral intake.
The horse is relatively earlier domesticated animal species. Domesticated horses have been selected for their ability of racing, robustness, and disease-resistance. As a result, the thoroughbred horse genome has been condensed many genotypes related to exercise ability. In recent years, with the advent of NGS technologies, many studies were concentrated on finding superior genetic species in the horse genome in terms of genomics. Consequently, GWAS (Genome-wide Association study) is applied to horse genome, then genetic marker is revealed for superior racing ability. In addition, RNA-Seq is utilized as a method for analyze of whole transcript profiling in specific samples. By using this approach, specific gene expression patterns and transcript sequences can be revealed in various samples such as each individual, before and after exercise state, and each tissue. DNA methylation, a strong factor that regulate gene expression without the change of DNA sequence, have got a lot of attention. In horse genome, exercise- or individual-specific DNA methylation patterns were detected, and could be useful to develop selective marker of superior horses. MicroRNAs inhibit gene expression, and transposable elements accounted for half of the mammalian genome. These two elements are the crucial factors in functional genomics, and could be applied to the selection of superior horses. As the functional genomics and epigenomics advance, then these technologies introduced in this paper were applied to select superior horses. In this paper, the studies for selection of superior horses through genetic technologies, and development possibilities of these studies were discussed.
Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.
Kim, Jae-Gon;An, Soo-Hyeon;Lee, Young-Su;Baik, Byeong-Ju;Cho, Eui-Sic
Journal of the korean academy of Pediatric Dentistry
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v.26
no.2
/
pp.350-364
/
1999
The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.
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