• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.702-709
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• 2003

Purpose : $IFN{\gamma}$ sentitizes many tumor cells to $TNF{\alpha}$ and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that $IFN{\gamma}$ and $TNF{\alpha}$ synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of $IFN{\gamma}$ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/CD95L autocrine circuit. In this study, we examined whether $IFN{\gamma}$ could affect $TNF{\alpha}$ and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. Methods : CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant $IFN{\gamma}$, $TNF{\alpha}$ and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V-PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. Results : $IFN{\gamma}$ or $TNF{\alpha}$ alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of $IFN{\gamma}$ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were non-specifically enhanced after treatment of $IFN{\gamma}$ without relation to sensitivity to $TNF{\alpha}$ and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of $TNF{\alpha}$ and CH-11-mediated apoptosis by $IFN{\gamma}$ in only sensitive cell lines. Conclusion : $IFN{\gamma}$ induced sensitization of $TNF{\alpha}$ and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.

• Proceedings of the Zoological Society Korea Conference
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• 1999.04a
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• pp.71.1-71
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• 1999

No Abstract, See Full Text

• Journal of Embryo Transfer
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• v.13 no.2
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• pp.179-190
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• 1998

Prolactin (PRL) surge in cycling rats at proestrous afternoon has previously been reported as an inducer of apoptotic cell death of luteal cells. This death-inducing action of PRL seeins unusual, because PRL can he categorized as a cell-survival factor, if other known physiological functions of PRL are taken into account. In this study, the apoptotic action of PRL was assessed in cultured cells prepared from rat luteal tissue and underlying molecular /cellular mechanism of PRL-induced luteolysis was analyzed. The latest crop of corpora lutea (CLs) were enucleated from rat ovaries at 18:00 h on the proestrous day before the next ovulation. Donor rats were pretreated with CB154, a dopamine agonist, in order to he exempted from the endogenous PRL surge. The harvested GLs were dispersed and cultured with or without PRL (2$\mu$g /ml) for 24 or 48 h. An addition of PRL to the culture medium changed the parameters indicative of cell death via apoptosis: a decrease in cell viability (MTT) and an increase in chromatin condensation. Most of the DNA breakdown in nuclei induced by PRL occurred in steroidogenic cells which were identified by 3$\beta$-HSD activity staining, and the number of 3$\beta$-HSD-positivecells were significantly decreased. Interestingly, most of the cells with an apoptotic nucleus adhered to one or more intact and seemingly non-steroidogenic cells. Because the expression of Fas has heen shown to be abundant in murine ovary, and Fas is known to have an exact physiological role in occurrence of apoptotic cell death, the membrane form-Fas ligand (rnFasL) was quantified in the cell lysate. An addition of PRL increased expression of mFasL. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, in place of PRL, enhanced the apoptotic parameters. Cumulatively, the apoptotic PRL action was addressed to cells unknown than steroidogenic lute~ cells. The most prohable candidate for the direct target cells is Tcells in the luteal tissue that can express mFasL in response to PRL.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.3
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• pp.195-200
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• 2002

Objective : To investigate the expression of apoptosis related proteins and apoptotic cells on the human ovarian follicles. Materials and Methods: Thirty five Formalin-fixed paraffin-embedded human ovarian tissue blocks were selected from the surgical pathology files of the department of pathology, College of Medicine, Yonsei University, for the period from 1996 to 1998. All specimen were from premenopausal women aged from $32{\sim}45$. Ovarian tissues were collected from the patients performing hysterectomy for benign uterine diseases. Immunohistochemical staining was performed for the detection of DNA fragmented cell, Bcl-2, Bax, Fas and Fas-ligand. Results: Bcl-2 and bax were not expressed on the surrounding cells and oocyte of the primary, primordial and preantral follicles. Fas and Fas-ligand (Fas-L) were not expressed on the surrounding cells on the primordial and primary follicles. But expressed on the surrounding granulosa cells and oocyte in the primordial and primary follicles. In the healthy follicles, Bcl-2 was expressed on the granulosa cells, however, Bax was not expressed. DNA fragmented cells were expressed on the inner granulosa cell layer of atretic follicles. Conclusion: Fas, Fas-ligand, and Bax may be responsible for the follicular atresia and Bcl-2 may be involved in the follicular survival in the human ovary.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.145-149
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• 2003

Background: Apoptosis has been implicated in pathogenesis of various disease. Apo-1/Fas (CD95) is one of the main pathway of apoptosis. To examine the possible relationship between Apo-1/Fas (CD95) and primary knee osteoarthritis, MvaI restriction length polymorphism (RFLP) in human Apo-1/Fas (CD95) gene was assessed. Methods: Genotype and allele frequencies in promoter region in the Apo-1/Fas (CD95) gene were studied by PCR-RFLP in 226 Korean controls and 148 Korean patients with primary knee osteoarthritis. Results: No statistically significant difference in the genotypic distribution and allelic frequencies was found between the control and the knee oateoarthritis patients. But in the severe grade (grade 3, 4) Kellgren-Lawrence score patients, the frequency of $MvaI^*1$ (G) allele was significantly decreased (P=0.0392) and the of $MvaI^*2$ (A) allele frequency was significantly increased (P=0.0473) compared to the normal controls. Conclusion: Apo-1/Fas (CD95) gene polymorphism is a part a determinant factor of severity in knee osteoarthritis, the patients with $MvaI^*2$ (A) allele is more severe radiologic progression. Further substantiation studies are needed in larger patient samples and various other apoptosis related genes to elucidate the mechanism of osteoarthritis, including the Fas ligand gene analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8877-8881
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• 2014

Background: Despite social gradients in adult smoking, the effects of socioeconomic position (SEP) on adolescent smoking is not well understood. This study examined effects of subjective SEP as well as the objective SEP on smoking among Korean adolescents. Materials and Methods: Data were obtained from the 2012 Korea Youth Risk Behavior Web-based Survey, a nationally representative sample of middle and high school students (38,221 boys; 35,965 girls). SEP was assessed by the Family Affluence Scale (FAS) and the self-rated household economic status. Relationships between SEP and smoking were analyzed by multivariate logistic regression. Results: The low perceived SEP for either the high or low FAS grade was related to an elevated likelihood of smoking in both genders. A significantly higher risk of smoking was found in boys of low perceived SEP in middle school (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.28-1.77 for high FAS, OR 1.55; 95% CI 1.21-1.98 for low FAS), and of low perceived SEP and high FAS in high school (OR 1.13; 95% CI 1.02-1.26). Among girls, an elevated risk of smoking was observed in middle school group with low perceived SEP and low FAS (OR 2.01; 95% CI 1.44-2.79) and in the high school group of low perceived SEP, regardless of FAS level (OR 1.34; 95% CI 1.14-1.57 for high FAS, OR 1.31; 95% CI 1.04-1.65 for low FAS). Conclusions: The relationship of subjectively perceived SEP with smoking is as important as objective SEP and more significant in Korean high school adolescents.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.123-133
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• 2003

Objectives : This study was designed to investigate the effects of Chungganhaeju-tang on expression of alcohol metabolizing enzymes, cell viability and alcohol-induced apoptosis. Materials and Methods : For this study, the human hepatoma cell line HepG2 was used. HepG2 cells were treated with ethanol-or acetaldehyde, chungganhaeju-tang, anti-Fas neutralizing antibody and were investigated by using quantitative RT-PCR, MTT and Trypan blue exclusion assays. Results : The results are summarized as follows: 1. Quantitative RT-PCR analysis demonstrated that ethanol-or acetaldehyde-mediated increase of ALDH gene expression was not affected by Chungganhaeju-tang treatment. 2, Ethanol-or acetaldehyde-induced apoptosis was remarkably inhibited by Chungganhaeju-tang in a dose-dependent manner. 3, Ethanol-or acetaldehyde-induced apoptosis was significantly blocked by anti-FasL neutralizing antibody, suggesting apoptosis induced by alcohol might be mediated by FasL/Fas signaling pathway. Conclusions : Taken all together, these results indicate that the FasL/Fas signaling plays a critical role in alcohol-induced apoptosis and Chungganhaeju-tang increases viability of liver cells by suppression of the FasL/Fas-mediated apoptosis-signaling pathway.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.162-169
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• 2022

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.

• Journal of Nutrition and Health
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• v.56 no.5
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• pp.523-536
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• 2023

Purpose: This study investigated the association between sleep problems and food allergies (FAs) in Chinese preschoolers and assessed whether there is a difference in this association among children with/without siblings. Methods: A cluster-stratified sampling approach was employed to select four districts in Chongqing based on demographic considerations. A total of 16 kindergartens (n = 966 parents) participated in this study. Parents completed the Children's Sleep Habits Questionnaire (CSHQ) and a standard FAs questionnaire. Analysis of covariance and multiple logistic regression were used to assess the associations between sleep problems and FAs after adjusting for relevant confounders. Results: The study found that 16.3% of children had FAs, with eggs, shellfish, and fruit being the most common allergenic foods. The prevalence of FAs was significantly higher in single children (20.63%) than in children with siblings (13.36%). A total of 70.39% of children had CSHQ scores above the clinical cut-off for sleep disorder. Factor analysis revealed five underlying dimensions from the CSHQ. Factor scores, except for the 'difficulty morning waking' factor, were not significantly different between the two groups. Remarkably, the factor scores of 'parasomnias' and 'sleep anxiety' were significantly higher when children had both siblings and FAs. For all subjects, the odds ratios (ORs) of FAs significantly increased with the presence of sleep disorder (OR, 2.35; 95% confidence interval [CI],1.50-3.68) and 'difficulty falling asleep' (OR, 1.34; 95% CI, 1.22-1.48). The subgroup analysis showed that the probability of FAs significantly increased with the 'difficulty falling asleep' (OR, 1.32 vs. 1.38) and sleep disorder (OR, 2.48 vs. 2.14) in children with and without siblings, respectively. The 'parasomnias' was positively associated only with children with siblings. Conclusion: This study suggests that children with siblings might be more susceptible to FAs when accompanied by certain sleep problems. Further studies are warranted to address the underlying dimensions and possible mediation effects of having siblings with sleep problems.

• Proceedings of the Korean Operations and Management Science Society Conference
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• 1992.04b
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• pp.436-443
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• 1992

Presented in the paper is a systematic approach to constructing a Petri net model of FAS (flexible assembly system). Petri net is widely used in modeling automated manufacturing systems. But, it found to be very difficult for an FA engineer to build a correct model of an FAS with Petri net symbols (ie, place, transition, and token) from the beginning. An automated manufacturing system in general is built from a set of "standard" hardware components. An FAS in particular is usually composed of assembly robots, work tables, conveyor lines, buffer storages, part feeders, etc. In the proposed modeling scheme, each type of standard resources is represented as a standard "module" which is a sub Petri net. Then, the model of a FAS can be conveniently constructed using the predefined modules the same way the FAS itself is built from the standard components. The network representation of a FAS is termed a JR-net (job resource relation net) which is easy to construct. This JR net is then mechanically converted to a formal Petri net (to simulate the behavior of the FAS). The proposed modeling scheme may easily be extended to the modeling of other types of automated manufacturing systems such as FMS and AS/RS.ch as FMS and AS/RS.