3.Alterations in Promoter Usage and Expression Levels of Insulin-like Growth Factor-II and H19 Genes in Cervical and Endometrial Cancer.
Chan LEE ; Seung Jo KIM ; Joong Yol NA ; Chang Suk PARK ; Sun Young LEE ; In Ho KIM ; Yu Kyoung OH
Cancer Research and Treatment 2003;35(4):314-322
PURPOSE: The biallelic expression of insulin-like growth factor-II (IGF2) and H19 has been reported to be associated with the progression of several tumors. Here, the promoter usage and expression levels of IGF2 and H19 are reported to be altered in cervical and endometrial cancers showing loss of imprinting (LOI). MATERIALS AND METHODS: The imprinting status of IGF2 and H19 was examined in 32 cervical carcinomas, their matched normal tissues, 13 endometrial cancer and 33 normal endometrial tissues. RESULTS: The LOI of IGF2 was observed in 7 of 18 (39%) and 1 of 13 (8.3%) informative cervical carcinomas and informative endometrial cancers, respectively. The LOI of the H19 gene was detected in 5 of 14 (36%) and in all 11 (100%) informative cervical carcinoma cases and informative endometrial cancer cases, respectively. The use of promoter P1 was observed in the LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2 imprinting (MOI), or in cervical and endometrial cancers. Unlike MOI tumors, some LOI tumors revealed a lack of IGF2 transcription from the promoter P3. The LOI tumors of IGF2 showed increased expression of the IGF2 level, but a down-regulation of the H19, relative to normal tissues, whereas the MOI tumors revealed no significant alterations. CONCLUSION: These results suggest that the promoter P1 could be involved in the biallelic expression of IGF2, and that the altered expression of the IGF2 and H19 levels might be associated with the progression of cervical and endometrial cancers that exhibit biallelic IGF2 expression.
Down-Regulation
;
Endometrial Neoplasms*
;
Female
;
Uterine Cervical Neoplasms
4.Expression of p53 and MHC Class I According to HPV Infection in Laryngeal Squamous Cell Carcinomas.
Chan Seung HWANG ; Hoon KIM ; Mi Kyung KIM
Journal of the Korean Cancer Association 1998;30(1):1-11
PURPOSE: We evaluated the HPV type 16, 18 infection and p53 expression and MHC class Iantigen expression, and analyzed he relationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas. MATERIALS AND METHODS: Thirty-nine cases of laryngeal squamous cell carcinomas and ten cases of laryngeal nodules were analyzed for detection of HPV DNA by in situ hybridization and the detection of p53 and MHC class I antigen by immunohistochemical technique. RESULTS: HPV DNA was detected in 10(26%), and p53 expression was detected in 19(49%) out of 39 cases in laryngeal squamous cell carcinomas. HPV positive cases showed 50% of p53 expression whereas HPV negative cases showed 48% expression. MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions, but there was no statistically significance. The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement. CONCLUSION: There was no reiationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas. Also these results suggest that MHC class I expression can make it possible to presume indirectly the malignant potentiality of the tumor.
Carcinoma, Squamous Cell*
;
DNA
;
Down-Regulation
;
In Situ Hybridization
5.The Protective Role of Estrogen by Down -regulation of Bax in Ceramide Induced Neuronal Cell Death.
Hee Sun CHAE ; Sung Su KIM ; Kyung Yong KIM ; Won Bok LEE
Korean Journal of Anatomy 2002;35(6):509-516
In the present study, we investigated effects of estrogen on cell death induced by ceramide in human neuroblastoma SK -N -SH. Estrogen, attenuated ceramide -induced cell death. To determine the molecular mechanism of protective effect of estrogen, we investigated the effect of estrogen on the increase of Bax by ceramide. Estrogen decreased Bax expression. Moreover, estrogen showed the inhibitory effect on the caspase activation by ceramide. These results suggest that estrogen attenuate ceramide -induced neuronal cell death by downregulation of Bax and subsequent inhibition of caspase activation.
Cell Death*
;
Down-Regulation
;
Estrogens*
;
Humans
;
Neuroblastoma
;
Neurons*
6.YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages.
Hye Jin OH ; Til Bahadur Thapa MAGAR ; Nirmala Tilija PUN ; Yunji LEE ; Eun Hye KIM ; Eung Seok LEE ; Pil Hoon PARK
Biomolecules & Therapeutics 2018;26(2):191-200
Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.
Chalcone
;
Down-Regulation
;
Macrophages*
;
NADPH Oxidase
;
Phosphorylation
;
Reactive Oxygen Species
7.Hyperosmotic Stimulus Down-regulates 1alpha, 25-dihydroxyvitamin D3-induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System.
Yu Shun TIAN ; Hyun Joo JEONG ; Sang Do LEE ; Seok Heui KONG ; Seung Ho OHK ; Yun Jung YOO ; Jeong Taeg SEO ; Dong Min SHIN ; Byung Wha SOHN ; Syng Ill LEE
The Korean Journal of Physiology and Pharmacology 2010;14(3):169-176
The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on 1alpha,25(OH)2D3-induced osteoclastogenesis was investigated in an osteoblast-preosteoclast co-culture system. Serial doses of sucrose were applied as a mechanical force. These hyperosmotic stimuli significantly evoked a reduced number of 1alpha,25(OH)2D3-induced tartrate-resistant acid phosphatase-positive multinucleated cells and 1alpha,25(OH)2D3-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor kappaB ligand (RANKL) and Runx2 expressions were down-regulated in response to 1alpha,25(OH)2D3. Knockdown of Runx2 inhibited 1alpha,25(OH)2D3-induced RANKL expression in osteoblastic cells. Finally, the hyperosmotic stimulus induced the overexpression of TonEBP in osteoblastic cells. These results suggest that hyperosmolarity leads to the down-regulation of 1alpha,25(OH)2D3-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.
Bone Remodeling
;
Coculture Techniques
;
Down-Regulation
;
Osteoblasts
;
RANK Ligand
;
Sucrose
8.Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial.
Xin-Tong YU ; Wen-Jia YANG ; Na ZHAO ; Rui-Long LIANG ; Xu-Qiu SUN ; Yue-Ping BI ; Yan-Yan MOU
Chinese Acupuncture & Moxibustion 2023;43(3):245-251
OBJECTIVE:
To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD).
METHODS:
A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups.
RESULTS:
Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05).
CONCLUSION
Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.
Humans
;
Acupuncture Therapy
;
Sleep
;
Acupuncture Points
;
Down-Regulation
;
Sleep Duration
9.Clinical characteristics and genetic analysis of a case of infantile Schaaf-Yang syndrome due to a heterozygous variant of MAGEL2 gene.
Jiaoe GONG ; Zhi JIANG ; Wenjing HU ; Hongmei LIAO ; Hua WANG
Chinese Journal of Medical Genetics 2023;40(10):1284-1287
OBJECTIVE:
To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS).
METHODS:
An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard.
RESULTS:
The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function.
CONCLUSION
The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.
Humans
;
Infant
;
Down-Regulation
;
Heterozygote
;
Mutation
;
Parents
;
Proteins
10.Induction of Apoptosis and Autophagy in UVB-Treated HaCaT Cells.
Sang Don YOON ; Won Ki BAEK ; Sang Pyo KIM ; Kyu Suk LEE ; Jae We CHO
Korean Journal of Dermatology 2013;51(8):600-607
BACKGROUND: UVB irradiation induces apoptosis or/and autophagy through several molecular pathways in keratinocytes. However, the precise molecular mechanism of UVB-induced autophagy is largely unknown in keratinocytes. OBJECTIVE: The purpose of this study was to investigate the molecular mechanisms of UVB-induced apoptosis and autophagy in HaCaT cell lines. METHODS: Cells were irradiated by UVB (Westinghouse FS-40 sunlamps) with various doses (0, 30, 60, 120, 240 mJ/cm2). The expression levels of caspase-3, Bax, Bcl2, Bcl-X(L) and LC3 were confirmed by Western blot analysis in UVB-irradiated HaCaT cell lines. Apoptotic cells were analyzed by PI staining, and autophagy cells were analyzed by immunofluorescent staining. RESULTS: The expression of Bcl-X(L) decreased from UVB 60 mJ/cm2 and Bcl2 decreased from UVB 240 mJ/cm2. The expression of caspase-3 was increased from UVB 120 mJ/cm2. These data showed that UVB-induced apoptosis is mediated by up-regulation of caspase-3 and down-regulation of Bcl2 and Bcl-X(L). Furthermore, the expression of LC3 increased from UVB 120 mJ/cm2. In addition, autophagy formation was observed in few fractions of apoptotic HaCaT cells in immunofluorescent staining; most apoptotic cells did not show autophagy formation. Moreover, autophagy formation inhibitor treatment induced a slight increment of apoptotic cell population under UVB irradiation. CONCLUSION: UVB irradiation induces not only apoptotic cell death but also autophagy formations; these events may create a defense mechanism for the prevention of apoptosis in UVB-treated HaCaT cells.
Apoptosis
;
Autophagy
;
Blotting, Western
;
Caspase 3
;
Cell Death
;
Cell Line
;
Down-Regulation
;
Keratinocytes
;
Up-Regulation