• Title/Summary/Keyword: Bcl I

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Expression of Bcl-2 in the epithelial lining and clinical findings of keratocystic odotogenic tumor (각화낭치성종양의 이장상피에서 Bcl-2 발현양상과 임상지표)

  • Lee, In-Hyuk;Choi, So-Young;Park, Ji-Hoon;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.3
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    • pp.161-168
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    • 2011
  • Purpose: The odontogenic keratocysts demonstrated a high recurrence rate and a biologically aggressive nature. This might be due to unknown factors inherent in the epithelium or enzymatic activity in the fibrous wall. Bcl-2 protein is characterized by its ability to inhibit apoptosis. The aim of this study was to evaluate the expression and distribution of bcl-2 in the OKCs, its possible relationship with the tumorous characteristics, such as the aggressive nature and high recurrence rate, and its usefulness to differentiate OKCs from dentigerous cysts. Materials and Methods: Formalin fixed paraffin-embedded tissue sections of 53 OKCs, and 44 dentigerous cyst were immunohistochemically analyzed quantitatively for the immunoreactivity of the bcl-2 protein with i-solution. Results: More Bcl-2 expression was observed in the OKCs (mean34.387%) than dentigerous cyst (mean11.144%) with statistical significance (P<0.001). Seventeen and 15 of the 32 OKCs in this study showed positivity in the basal layer and basal/suprabasal layers, respectively. In dentigerous cyst, 2 of 3 showed positivity in the basal cell layer. Conclusion: Considering that bcl-2 over expression may lead to the increased survival of epithelial cells, this study demonstrated a possible relationship between the aggressive nature of OKC and the intrinsic growth potential of its lining epithelium. Furthermore, the basal/suprabasal distribution of bcl-2 positive cells was observed in some OKCs, which might have a significant impact on the behavior of cysts. The bcl-2 expression of OKCs can be useful for differentiating OKCs from dentigerous cysts.

Expression of bcl-2, p53 Protein and Aggressiveness in Thymic Epithelial Tumor (흉선상피종에서 bcl-2, p53 단백의 발현과 악성도)

  • 조성래;전도환
    • Journal of Chest Surgery
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    • v.32 no.8
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    • pp.726-731
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    • 1999
  • Background: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. Material and Method: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. Result: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). Conclusion: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.

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Polymorphisms of the NR3C1 gene in Korean children with nephrotic syndrome (한국 신증후군 환아에서 NR3C1 유전자 다형성 분석)

  • Cho, Hee Yeon;Choi, Hyun Jin;Lee, So Hee;Lee, Hyun Kyung;Kang, Hee Kyung;Ha, Il Soo;Choi, Yong;Cheong, Hae Il
    • Clinical and Experimental Pediatrics
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    • v.52 no.11
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    • pp.1260-1266
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    • 2009
  • Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

Downstream Genes Regulated by Bcl2l10 RNAi in the Mouse Oocytes

  • Kim, Eun-Ah;Kim, Kyeoung-Hwa;Lee, Hyun-Seo;Lee, Su-Yeon;Kim, Eun-Young;Seo, You-Mi;Bae, Jee-Hyeon;Lee, Kyung-Ah
    • Development and Reproduction
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    • v.15 no.1
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    • pp.61-69
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    • 2011
  • Previously, we have shown that Bcl2l10 as a member of Bcl-2 family, key regulators of the apoptotic process, is dominantly expressed in oocytes of ovary but several member of the Bcl-2 family are not expressed in oocytes. Recent our studies had been processed about roles and regulatory mechanisms of Bcl2l10 in oocytes. Microinjection of Bcl2l10 RNAi into the cytoplasm of germinal vesicle oocytes resulted in metaphase I (MI) arrest and exhibited abnormalities in their spindles and chromosome configurations (Yoon et al., 2009). The present study was conducted to elucidate the downstream genes regulated by Bcl2l10 and signaling networks in Bcl2l10 RNAi microinjected oocytes by using microarray analysis. Surprisingly, we found that a large proportion of genes regulated by Bcl2l10 RNAi were involved in the cell cycle and actin skeletal system regulation as important upstream genes of Bcl2l10. Among the transcripts with highly significant fold changes more than 2-fold, Tpx2 and Cep192 are 16.1- and 8.2-fold down regulated respectively by Bcl2l10 RNAi. Tpx2 and Cep192 are known as cofactors that control Aurora A kinase activity and localization. Therefore, we concluded that Bcl2l10 may have important roles during oocyte meiosis as functional upstream regulator of Tpx2 and Cep192.

Research on the Anti-Breast Cancer and Anti-Inflammatory Effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum (청간해울탕(淸肝解鬱湯)과 십륙미유기음(十六味流氣飮)의 유방암에 대한 항암, 항염 효능 연구)

  • Ryu, Hyo-Kyung;Jung, Min-Jae;Cho, Seong-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.35 no.3
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    • pp.1-23
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    • 2022
  • Objectives: The purpose of this study is to evaluate anti-breast cancer and anti-inflammatory effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum. Methods: MDA-MB-231 cells were used to measure cytotoxicity, Reactive oxygen species (ROS) production, protein expression amounts of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Cytochrome C Caspase-3, Caspase-7, Caspase-9, Poly ADP-ribose polymerase (PARP), Nuclear factor erythroid-2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD (P) H Quinone Oxidoreductase 1 (NQO1) to evaluate the anti-breast cancer effects of Chungganhaewool-tang (CHT) and Shipyeukmiyeugi-eum (SYE), and THP-1 cells, differentiated into macrophage and induced inflammation with Lipopolysaccharide (LPS), were used to measure production amounts of ROS, Nitric oxide (NO), and protein expression amounts of Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX-2), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) to evaluate the anti-inflammatory effects of CHT and SYE. Results: CHT and SYE reduced MDA-MB-231 cell counts, increased protein expression of Bax and Cytochrome C, and decreased protein expression of Bcl-2, Bcl-xl. The protein expression amounts of Caspase-3, 7, and 9 decreased, but amounts of the active form, cleaved Caspase-3, 7, and 9, increased. In addition, PARP protein expression decreased, the amount of PARP protein in the cleaved form increased, and the amount of protein expressions of Nrf2 and HO-1 decreased, but NQO1 showed no significant difference. In THP-1 cells CHT and SYE reduced ROS and NO, and reduced protein expressions of iNOS, COX-2, IL-1, and TNF-α, but only SYE groups reduced IL-6. Conclusions: This study suggests that CHT and SYE have potential to be used as treatments for breast cancer.

Performance Test of 4Cl Beamline for Protein Solution Scattering at the PLS (용액상의 단백질 구조 분석을 위한 PLS 4Cl빔라인의 성능 테스트)

  • Yu Chung-Jong;Kim Jehan;Kim Kwang-Woo;Kim Ghyung-Hwa;Lee Heung-Soo;Ree Moonhor;Kim Kyung-Jin
    • Journal of the Korean Vacuum Society
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    • v.14 no.3
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    • pp.138-142
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    • 2005
  • We tested performance of the 4C1 beamline for analyzing structures of proteins in solution using small angle X-ray scattering (SAXS) at the Pohang Light Source(PLS). Structurally well-known proteins such as lysozyme and $Bcl-XL(\vartriangle TM/\vartriangle loop)$ were used for the study. Low resolution solution structures of lysozyme and $Bcl-XL(\vartriangle TM/\vartriangle loop)$ were obtained at a resolution of at least i.2 nm, and the structures were basically same as those calculated from the crystal structures of the proteins. We also used $Bcl-XL(\vartriangle TM/\vartriangle loop)$ with a long flexible loop attached [$Bcl-XL(\vartriangleTM))$] and obtained significantly different data from $Bcl-XL(\vartriangle TM/\vartriangle loop)$, although the electron density map of the loop is known to be invisible from the crystal structure of $Bcl-XL(\vartriangleTM))$. We confirm that SAXS experiment is a powerful tool for the structural study of proteins in solution and the 4Cl beamline at the PLS is well-equipped and suitable for the protein solution SAXS experiment.

Mechanisms of Siegesbeckia Glabrescens-induced Smooth Muscle Cell Apoptosis: Role of iNOS and PKC${\alpha}$ (희첨의 iNOS 발현과 PKC${\alpha}$ 억제를 통한 혈관평활근세포의 apoptosis 유도)

  • Lee, Seung-Yeul;Jun, Soo-Young;Kim, Jong-Bong;Jang, Hyo-Oil;Kim, Gil-Whon;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1233-1240
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    • 2006
  • We have recently demonstrated that Siegesbeckia glabrescens(SG), a herbal medicine, induces apoptosis via nitric oxide(NO) production in human aortic smooth muscle cells(HASMCS). However, the molecular pathways involved in SG-mediated apoptosis are not fully understand. In the present study, we investigated the cellular mechanisms of SG-induced apoptosis in HASMCS. SG induced NO production through inducible nitric oxide synthase(iNOS) induction. The apoptotic effect of SG was attenuated by L-NNA, a NOS inhibitor. In the presence of L-NNA, the degradation of procaspase-3 by SG was inhibited. SG treatment induced a decrease in Bcl-2 expression but did not affect the expression of Bax. In addition, SG treatment evoked both down-regulation of PKC ${\alpha}$ and inhibition of PKC ${\alpha}$ phosphorylation. These downregulations were reversed by addition of L-NNA. It seems likely to De a downregulation of PKC${\alpha}$ due to long term treatment with PMA. Taken together, these results suggest that apoptotic effects of SG may be due to NO production via iNOS mRNA expression. Furthermore, Bcl-2 and PKC${\alpha}$ downregulation, and caspase-3 activation may be involved in the mechanisms for apoptotic effects by SG.

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

  • Banjerdpongchai, Ratana;Khaw-on, Patompong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7537-7542
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    • 2013
  • Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

Prognostic Value of the Expression of p53 and bcl-2 in Non-Small Cell Lung Cancer (비소세포폐암에서 p53과 bcl-2의 발현이 예후에 미치는 영향)

  • Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Keum, Joo-Seob;Kong, Gu;Lee, Jung-Dal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.962-974
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    • 1998
  • Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

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Capacitively Coupled Dry Etching of GaAs in BCl3/N2 Discharges at Low Vacuum Pressure (저진공 축전 결합형 BCl3/N2 플라즈마를 이용한 GaAs의 건식 식각)

  • Kim, Jae-Kwon;Park, Ju-Hong;Lee, Sung-Hyun;Noh, Ho-Seob;Joo, Young-Woo;Park, Yeon-Hyun;Kim, Tae-Jin;Lee, Je-Won
    • Korean Journal of Materials Research
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    • v.19 no.3
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    • pp.132-136
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    • 2009
  • This study investigates GaAs dry etching in capacitively coupled $BCl_3/N_2$ plasma at a low vacuum pressure (>100 mTorr). The applied etch process parameters were a RIE chuck power ranging from $100{\sim}200W$ on the electrodes and a $N_2$ composition ranging from $0{\sim}100%$ in $BCl_3/N_2$ plasma mixtures. After the etch process, the etch rates, RMS roughness and etch selectivity of the GaAs over a photoresist was investigated. Surface profilometry and field emission-scanning electron microscopy were used to analyze the etch characteristics of the GaAs substrate. It was found that the highest etch rate of GaAs was $0.4{\mu}m/min$ at a 20 % $N_2$ composition in $BCl_3/N_2$ (i.e., 16 sccm $BCl_3/4$ sccm $N_2$). It was also noted that the etch rate of GaAs was $0.22{\mu}m/min$ at 20 sccm $BCl_3$ (100 % $BCl_3$). Therefore, there was a clear catalytic effect of $N_2$ during the $BCl_3/N_2$ plasma etching process. The RMS roughness of GaAs after etching was very low (${\sim}3nm$) when the percentage of $N_2$ was 20 %. However, the surface roughness became rougher with higher percentages of $N_2$.