• Title/Summary/Keyword: BCL 6

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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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High Density Planar Inductively Coupled Plasma Etching of GaAs in BCl$_3$-based Chemistries (BCl$_3$ 기반 가스를 이용한 GaAs의 고밀도 평판형 유도결합 플라즈마 식각)

  • ;;;;;;S.J. Pearton
    • Journal of the Korean institute of surface engineering
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    • v.36 no.5
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    • pp.418-422
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    • 2003
  • 평판형 유도결합 플라즈마 식각장비(inductively coupled plasma etcher)를 이용하여 각종 공정조건들에 따른 GaAs의 식각특성을 연구하였다. 공정변수들은 ICP 소스파워(0-500 W), RIE 척파워(0-150 W), 가스 종류($BCl_3$, $BCl_3$/Ar, $BCl_3$/Ne) 및 가스혼합비였다. $BCl_3$ 가스만을 이용하여 GaAs를 식각한 경우보다 25%의 Ar이나 Ne같은 불활성 기체를 혼합한 $15BCl_3$/5Ar, $15BCl_3$/5Ne 가스를 이용한 경우의 식각률이 더 우수한 것을 확인하였다. 그리고 50% 이하의 Ar이 혼합된 $BCl_3$/Ar의 경우는 높은 식각률 (>4,000 $\AA$/min)과 평탄한 표면(RMS roughness : <2 nm)을 얻을 수 있었지만 지나친 양(>50%)의 Ar의 혼합은 오히려 표면을 거칠게 하거나 식각률을 떨어뜨리는 결과를 가져왔다. 그리고 20 sccm $BCl_3$, 100 W RIE 척파워, 300 W ICP 소스파워, 공정압력이 7.5 mTorr인 조건에서의 GaAs의 식각결과는 아주 우수한 특성(식각률: ∼ 4,000, $\AA$/min, 우수한 수직측벽도: >$87^{\circ}$, 평탄한 표면: RMS roughness : ∼0.6 nm)을 나타내었다.

Quercetin Down-regulates IL-6/STAT-3 Signals to Induce Mitochondrial-mediated Apoptosis in a Non-small-cell Lung-cancer Cell Line, A549

  • Mukherjee, Avinaba;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.19-26
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    • 2015
  • Objectives: Quercetin, a flavonoid compound, has been reported to induce apoptosis in cancer cells, but its anti-inflammatory effects, which are also closely linked with apoptosis, if any, on non-small-cell lung cancer (NSCLC) have not so far been critically examined. In this study, we tried to determine if quercetin had any demonstrable anti-inflammatory potential, which also could significantly contribute to inducing apoptosis in a NSCLC cell line, A549. Methods: In this context, several assays, including cytotoxicity, flow cytometry and fluorimetry, were done. Gene expression was analyzed by using a western blot analysis. Results: Results revealed that quercetin could induce apoptosis in A549 cells through mitochondrial depolarization by causing an imbalance in B-cell lymphoma 2/Bcl2 Antagonist X (Bcl2/Bax) ratio and by down-regulating the interleukine-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. An analysis of the data revealed that quercetin could block nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) activity at early hours, which might cause a down-regulation of the IL-6 titer, and the IL-6 expression, in turn, could inhibit p-STAT3 expression. Down-regulation of both the STAT3 and the NF-${\kappa}B$ expressions might, therefore, cause down-regulation of Bcl2 activity because both are major upstream effectors of Bcl2. Alteration in Bcl2 responses might result in an imbalance in the Bcl2/Bax ratio, which could ultimately bring about mitochondria mediated apoptosis in A549 cells. Conclusion: Overall, the finding of this study indicates that a quercetin induced anti-inflammatory pathway in A549 cells appeared to make a significant contribution towards induction of apoptosis in NSCLC and, thus, may have a therapeutic use such as a strong apoptosis inducer in cancer cells.

Pulsed DC $BCl_3/SF_6$ 플라즈마를 이용한 GaAs와 AlGaAs의 선택적 식각에 관한 연구

  • Choe, Gyeong-Hun;Kim, Jin-U;No, Gang-Hyeon;Sin, Ju-Yong;Park, Dong-Gyun;Song, Han-Jeong;Lee, Je-Won
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.67-67
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    • 2011
  • Pulsed DC $BCl_3/SF_6$ 플라즈마를 사용하여 GaAs와 AlGaAs의 건식 식각을 연구하였다. 식각 공정 변수는 가스 유량 (50~100 % $BCl_3$ in $BCl_3/SF_6$), 펄스 파워 (450~600 V), 펄스 주파수 (100~250 KHz), 리버스 시간 (0.4~1.2 ${\mu}s$)이었다. 식각 공정 후 표면 단차 측정기 (Surface profiler)를 사용하여 표면의 단차와 거칠기를 분석하였다. 그 결과를 이용하여 식각률 (Etch rate), 표면거칠기 (Surface roughness), 식각 선택비 (Selectivity)와 같은 특성 평가를 하였다. 실험 후 주사 현미경 (FE-SEM, Field Emission Scanning Electron Microscopy)을 이용, 식각 후 시료의 단면과 표면을 관찰하였다. 실험 결과에 의하면 1) 18 sccm $BCl_3$ / 2 sccm $SF_6$, 500 V (Pulsed DC voltage), 0.7 ${\mu}s$ (Reverse time), 200 KHz (Pulsed DC frequency), 공정 압력이 100 mTorr인 조건에서 GaAs와 Al0.2Ga0.8As의 식각 선택비가 약 48:1로 우수한 결과를 나타내었다. 2) 펄스 파워 (Pulsed DC voltage), 리버스 시간(Reverse time), 펄스 주파수(Pulsed DC frequency)의 증가에 따라 각각 500~550 V, 0.7~1.0 ${\mu}s$, 그리고 200~250 KHz 구간에서 AlGaAs에 대한 GaAs의 선택비가 감소하게 되는 것을 알 수 있었다. 이는 척 (chuck)에 인가되는 전류와 파워를 증가시키고, 따라서 GaAs의 식각률이 크게 증가했지만 AlGaAs 또한 식각률이 증가하게 되면서 GaAs에 대한 식각 선택비가 감소한 것으로 생각된다. 3) 표면 단차 측정기와 주사전자현미경 사진 결과에서는 GaAs의 경우 10% $SF_6$ (18 sccm $BCl_3$ / 2 sccm $SF_6$)가 혼합된 조건에서 상당히 매끈한 표면 (RMS roughness < 1.0 nm)과 높은 식각률 (~0.35 ${\mu}m$/min), 수직의 식각 측벽 확보에서 매우 좋은 결과를 보여주었다. 또한 같은 공정 조건에서 AlGaAs는 식각이 거의 되지 않은 결과 (~0.03 ${\mu}m$/min)를 보여주었다. 위의 결과들을 종합해 볼 때 Pulsed DC $BCl_3/SF_6$ 플라즈마는 GaAs와 AlGaAs의 선택적 식각 공정에서 매우 우수한 공정 결과를 나타내었다.

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Expression of Bcl-2 and Caspase-3 Proteins Related to Apoptosis in Human Leukemia K-562 Cells

  • Chang Jeong-Hyun;Kwon Heun-Young
    • Biomedical Science Letters
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    • v.11 no.3
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    • pp.281-287
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    • 2005
  • Although actinomycin D (AMD) is known to induce apoptotic cell death to various cell lines, the mechanism of apoptosis induced by AMD is still unclear. Understanding this mechanism may improve its therapeutic efficacy. The present study has been performed to elucidate expression of Bcl-2 and Caspase-3 proteins related to apoptosis in human leukemia K-562 cells. Five different assays were performed in this study; DNA fragmentation analysis by agarose gel electrophoresis, quantitative assay of fragmented DNA, morphological assessment of apoptotic cells, quantification of apoptosis by annexin V (AV) and propidium iodide (PI) staning, and expression of Bcl-2 and Caspase-3 proteins by the western blot analysis. The number of apoptotic cells and amount of fragmented DNA in this cell line treated with AMD was increased at 6 hour. DNA ladder pattern was also appeared at 6 hour. The expression of Bcl-2 was decreased, and disappeared from 12 hours after AMD treatment. Precursor of Caspase-3 was degraded, and 20 kDa cleavage products were detected. These results suggest that AMD induced apoptosis of K-562 cells is Caspase-3-dependent fashion, and this apoptosis is related to the degradation of Bcl-2 proteins.

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Effects of Bambusae Caulis in Liquamen on Blood Sugar in db/db Mice (죽력이 db/db mouse의 혈당강하에 미치는 영향)

  • Cheong Ki Sang;Choi Chan Hun;Jang Kyeong Seon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.177-182
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    • 2003
  • This study was carried out to understand the effects of Bambusae Caulis in Liquamen on blood sugar in the db/db mice. Refined Bambusae Caulis in Liquamen C. D(BCL.C. D)manufactured by high temperature production process and Bambusae Caulis in Liquamen(H-BCL) manufactured & distributed by HANLIM PHARM.COM., LTD were used. The Bambusae Caulis in Liquamen extracted from bamboo charooal manufacturing process was filtered and refined. The effects of Bambusae Caulis in Liquamen were administered orally to mice for 6weeks and its anti-diabetic effect examined. The effects of BCL.C. D and H-BCL were observed in terms of blood sugar. creatinine. BUN and GPT in db/db mice. The results were as follows : The amount of glucose was slightly decreased (P<0.05) in the B CL.C-treated groups compared with the control. The amount of glucose was significantly decreased (P<0.01) in the BCL.D and H-BCL-treated groups compared with the control. The amount of creatinine did not show any differences among four groups. The amount of blood urea nitrogen did not show any differences in the case of BCL.C-treated groups. but observed significant decrease in the case of BCL.D and H-BCL-treated groups. The amount of GPT did not show any differences in the case of BCL.D-treated groups. but observed significant increase in the case of BCL.C and H-BCL-treated groups.

Lack of Relation of AKAP12 with p53 and Bcl-2 in Colorectal Carcinoma

  • Suren, Dinc;Yildirim, Mustafa;Alikanoglu, Arsenal Sezgin;Kaya, Vildan;Yildiz, Mustafa;Dilli, Utku Donem;Sezer, Cem
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3415-3418
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    • 2014
  • Background: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. Materials and Methods: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. Results: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). Conclusions: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas.

Anti-apoptotic effect by Bcl-2 in UVB-irradiated keratinocytes.

  • Takahashi, Hidetoshi;Honma, Masaru;Ishida-Yamamoto, Akemi;Namikawa, Kazuhiko;Miwa, Akiko;Okado, Haruo;Kiyama, Hiroshi;Iizuka, Hajime
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.225-228
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    • 2002
  • Bcl-2 is a member of large bcl-2 family and protects cells from apoptosis. Using bcl-2-expressing adenovirus vector (Ad-bc1-2), we investigated the effect of bc1-2 on UVB-induced apoptosis. Adenovirus vector efficiently introduced bc1-2 gene in cultured normal mouse keratinocytes (NMK cells); almost all NMK cells (lx10$^{6}$ ) were transfected at Ixl0$^{8}$ PFU/ml. Bcl-2-transfected NMK cells were significantly resistant to UVB-induced apoptosis with the suppressive effect dependent on bcl-2-expression level. Following UVB irradiation caspase 8, 3, 9 activities were stimulated in NMK cells, while in bc1-2-transfected cells, only caspase 8, but not caspase 3 or 9 activities were stimulated. In order to investigate the effect of bc1-2 in vivo, topical application of Ad-bc1-2 on tape-stripped mouse skin was performed. Following the application, Bc1-2 was efficiently overexpressed in almost all viable keratinocytes. The expression was transient with the maximal expression of Bc1-2 at 1st day following the application of lxl0$^{9}$ PFU in 200ml. The introduced Bc1-2 remained at least for 6 days. UVB irradiation (1250 J/m$^2$) induced apoptosis within 12 h and the maximal effect was observed at 24 h in control mouse skin. Bc1-2-transfected mice skin were resistant to UVB-induced apoptosis. Topical application of empty adenovirus vector alone had no effect on Bc1-2 expression or UVB-induced apoptosis. These results indicate that adenovirus vector is an efficient gene delivery system into keratinocytes and that Bcl-2 is a potent inhibitor of UVB-induced apoptosis both in vitro and in vivo.

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The Effect of Swimming and Minocycline on Motor Function and Expression of Bcl-2 after Spinal Cord Injury in the Rats (미노싸이클린과 수영훈련이 척수손상 흰쥐의 운동기능 및 Bcl-2발현에 미치는 영향)

  • Ha, Mi-Sook;Ha, Bae-Jin
    • Journal of Life Science
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    • v.19 no.10
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    • pp.1489-1494
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    • 2009
  • This study was designed to investigate the effects of swimming and minocycline on motor function recovery and Bcl-2 expression after spinal cord injury (SCI) in rats. After operation, neurological motor behavior test (BBB scale) on days 1, 4, 7, 10, and 14 were tested. Western blot and immunohistochemical assessment (Bcl-2) were performed on day 14. BBB scale started to show a statistically significant difference on day 7 (p<0.05). On day 14, it showed the most significant (p<0.05) difference. Expression of Bcl-2 increased in all the experimental groups. In particular, the highest expression of Bcl-2 appeared in the swimming and minocycline groups. Based on these results, minocycline and swimming were the most effective factors in the motor behavior function and immunohistochemical assessment of SCI rats.

The Role of Fas in Radiation Induced Apoptosis in vivo (방사선에 의한 Apoptosis에서 Fas의 역할)

  • Kim, Sung-Hee;Seong, Jin-Sil;Seong, Je-Kyung
    • Radiation Oncology Journal
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    • v.20 no.3
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    • pp.246-252
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    • 2002
  • Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.