• Toxicological Research
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• 제18권4호
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• pp.411-416
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• 2002

Apoptosis, or programmed cell death, is a genetically regulated pathway that is altered in many cancers. Overexpression of bcl-2 leads to resistance to apoptosis and promotes tumorigenesis. To determine the effect of bcl-2 antisense treatment in human lung cancer cell lines, a 20 mer full phosphorothioate oligonucleotide (ODN) targeted at the coding region of the bcl-2 mRNA was synthesized. Western blot analyses were used to examine bcl-2 protein level in five human non-small cell lung cancer (NSCLC) cell lines (NCI-H226, SK-MES-1 NCI-H358, NCI-H522 and NCI-Hl 299) and four human small cell lung cancer (SCLC) cell lines (NCI-H69, NCI-H4l7, HCC-2108 and SW2). Three out of five NSCLC (NCI-H226, SK-MES-1 and NCI-Hl 299) and all of SCLC cell lines expressed Bcl-2 protein. Treatment of these cell with antisense ODN for 48 hours reduced their viability and Bcl-2 protein level. As a conclusion, bcl-2 antisense treatment appears reduction of the Bcl-2 protein levels and cytotoxic effect including apoptosis in human lung cancer cell lines.

• Journal of Oral Medicine and Pain
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• 제24권2호
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.448-453
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• 1999

In ginsenoside Rh2-treated rat glioma C6Bu-1 cells, apoptotic morphological changes, such as cell shrinkage, chromatin condensation and pyknosis were confirmed by means of electron microscopy. To evaluate whether induction of apoptosis by ginsenoside Rh2 is mediated by the members of Bcl-2 family, we first established C6Bu-1 cells overexpressing Bcl-2. It was demonstrated that the expression of Bcl-2, Bcl-xL, and Bax was not altered in ginsenoside Rh2-treated C6Bu-1 overexpressing C6Bu-1 cells failed to prevent from ginsenoside Rh2-induced cell death. These results suggest the existence of other apoptotic pathway that requires induction of apoptosis by ginsenoside Rh2 rather than the pathway through Bcl-2, $Bcl-x_{L}$ or Bax in C6Bu-1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2387-2391
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• 2013

Resistance to apoptosis is a major obstacle preventing effective therapy for malignancies. Bcl-2 plays a significant role in inhibiting apoptosis. We reconstructed a stable human Bcl-2 transfected cell line, BIU87-Bcl-2, that was derived from the transfection of human bladder carcinoma cell line BIU87 with a plasmid vector containing recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. A cell line transfected with the plasmid alone [pcDNA3.1(+)-neo] was also established as a control. BIU87 and BIU87-neo proved sensitive to adriamycin induced apoptosis, while BIU87-Bcl-2 was more resistant. In view of the growing evidence that NF-${\kappa}B$ may play an important role in regulating apoptosis, we determined whether Bcl-2 could modulate the activity of NF-${\kappa}B$ in bladder carcinoma cells. Stimulation of BIU87, BIU87-neo and BIU87-Bcl-2 with ADR resulted in an increase expression of NF-${\kappa}B$ (p<0.001). The expression of NF-${\kappa}B$ in BIU87-Bcl-2 was higher than in the other two cases, with a concomitant reduction in the $I{\kappa}B{\kappa}$ protein level. These results suggest that the overexpression of Bcl-2 renders human bladder carcinoma cells resistant to adriamycin-induced cytotoxicity and there is a link between Bcl-2 and the NF-${\kappa}B$ signaling pathway in the suppression of apoptosis.

• Journal of Korean Neurosurgical Society
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• 제29권4호
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• pp.485-490
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• 2000

Objective : To study the expression of apoptosis and bcl-2 in the astrocytic tumors. Patients and Methods : A total of thirty-eight astrocytomas(9 cases in low grade astrocytoma, 12 cases in anaplastic astrocytoma and 17 cases in glioblastoma) are included in this study. Immunohistochemical stain for bcl-2 using monoclonal antibody, in situ end labelling technique for apoptosis were used. Results : The malignant group(anaplastic astrocytoma and glioblastoma) showed significantly higher apoptosis positive index(PI) compared to the benign group(low grade astrocytoma)(1.35 vs 0.14). However apoptosis PI and bcl-2 PI were not significantly different among three groups. Correlation between apoptosis PI and bcl-2 PI was not statistically significant(p=0.58). Conclusion : This result suggest that apoptosis PI and bcl-2 PI are not related the degree of malignancy in astrocytic neoplasm, but apoptosis PI in malignant group was higher possibly due to greater DNA damage.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1037-1041
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• 2013

Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases.

• Journal of Chest Surgery
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• 제31권10호
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• pp.924-927
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• 1998

연구배경 : 심근의 허혈 또는 재관류에 의한 세포사에는 괴사 이외에 세포고사가 존재함이 알려져 있다. Bcl-2 단백은 세포질에 존재하는 단백으로 세포고사를 억제하는 기능을 하며 정상심근에서는 발현되지 않으나 심근경색의 급성기에서 발현됨이 보고되어 있다. 본 연구는 가토 허혈-재관류 심근에서 Bcl-2 단백의 발현 여부와 재관류의 시간에 따른 발현의 변화를 알아보고자 하였다. 방법: 평균 무게가 2.9Kg(1.5-4.8Kg)인 가토 39마리를 이용하였다. 허혈-재관류 모델의 각 실험동물에서 좌전하행지를 30분간 결찰한 다음 1, 4, 8, 12, 24시간, 3, 7일 동안 재관류시켰다. 이후 즉시 실험동물을 희생시킨 다음 심장을 적출하여 심근조직을 얻고 10% buffered formalin에 고정하였다. Bcl-2 단백의 발현은 파라핀에 포매된 조직에서 단일클론항체를 이용한 면역조직화학적 염색으로 확인하였다. 결과: 허혈-재관류 심근 중 12, 24시간, 3일 재관류군에서 Bcl-2 단백의 발현을 관찰할 수 있었으며, 특히 24시간 재관류 심근에서 잘 관찰되었다. Bcl-2 양성염색의 심근세포는 위험부위의 구제심근에서 관찰되었다. 결론: Bcl-2 단백은 심근의 허혈-재관류에서 급성기의 비교적 후기에 발현되며, 이는 재관류 초기에서 보다는 후기에서 세포고사를 억제하는데 일부 역할을 할 것으로 사료된다.

• 대한전자공학회:학술대회논문집
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• 대한전자공학회 1998년도 하계종합학술대회논문집
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• pp.409-412
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• 1998

BCl/sub 3/ 및 Cl/sub 2/ 반응가스를 사용하여 RIE 장치로 GaN의 건식식각을 연구하였다. RF 전력, 반응가스의 유량 및 반응가스의 혼합비 등의 변화에 따른 최적의 식각공정 조건 및 결합특성을 연구하였다. RF 전력에 따른 GaN의 식각율은 챔버압력 25mTorr, BCl/sub 3/ 유량 40 sccm의 조건에서 RF 전력이 100W일때 17nm/min을 얻었다. BCl/sub 3/의 유량에 따른 식각율은 RF 전력 100W 챔버압력 20mTorr, Cl/sub 2/ 유량 5sccm의 조건에서 BCl/sub 3/ 유량이 40 sccm일때 65nm/min을 얻었다. Cl/sub 2//BCl/sub 3/ 혼합가스 비율에 따른 식각율은 Cl/sub 2/ 유량을 5sccm으로 고정하고 BCl/sub 3/ 유량을 변화시켰을때 RF 전력 100W 및 챔버압력 20mTorr의 조건에서 혼합비가 0.25일때 50nm/min을 얻었다. RF 전력에 따른 PR의 식각율은 챔버압력 25mTorr, Cl/sub 2/ 유량 0 sccm 및 BCl/sub 3/ 유량 40 sccm의 조건에서 RF 전려이 100W일때 15nm/min을 얻었다. 또한, 챔버압력 20mTorr, Cl/sub 2/ 유량 5 sccm 및 BCl/sub 3/ 유량 20sccm의 조건에서 RF 전력이 100W 일때 82nm/min을 얻었다.

• Journal of Gastric Cancer
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• 제9권3호
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• pp.88-95
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• 2009

목적: 세포자멸사의 중요인자인 p53과 bcl-2의 개별발현 및 동시 발현이 갖는 위선암의 예후 인자로서의 역할과 생존율에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 1999년 12월에서 2007년 7월까지 위선암으로 분당제생병원 외과에서 근치적 위절제술을 시행 받은 238명의 환자들을 대상으로 자료의 후향적 분석을 시행하였다. p53과 bcl-2의 발현은 DAKO사의 Envision kit로 면역조직화학 염색을 하여 발현군을 양성으로 정의하였다. 결과: 전체 환자 중 p53은 149예(62.5%)에서 발현되었으며, 다른 임상병리학적 예후 인자와의 상관관계를 조사한 결과 세포분화도(P=0.028), TNM 병기(P<0.001)에서 유의성을 나타냈다. bcl-2은 29예(12.2%)가 발현되었으며, TNM 병기(P=0.005)에서 유의성을 나타냈다. 단변량 생존율 분석을 통해 p53과 bcl-2는 생존율 감소에 영향이 있으며, 다변량 생존율 분석을 통해 p53은 독립적 예후 인자로서의 확인되었다. 또한 두 단백의 동시 발현군도 TNM 병기(P=0.002)와 의미 있는 상관관계를 보였으며, 개별 발현 때보다 동시 발현 시 유의한 생존율 감소를 보였다(P<0.001). 결론: p53과 bcl-2의 개별 발현은 나쁜 예후를 나타내며, 이들의 동시 발현은 더욱 나쁜 예후를 나타냈다. 그러나 bcl-2는 다변량 분석에서 독립 예후인자로서 의미는 부족하여 더 많은 분석을 통해 명확히 할 필요가 있겠다.

• 생물정신의학
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• 제4권2호
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• pp.211-217
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• 1997

The Bcl-2 protein has been shown to block apoptosis induced by a variety of stimuli. We have performed the experiments which cell death can be blocked by the bcl-2 proto-oncogene under moderate(50-100mM) or high ethanol treatment(400-600mM). As a result of morphological changes, and MTT assay, cell death was blocked by Bcl-2 under 100mM ethanol. However, the results of DNA fragmentation and RT-PCR(ICE, and CPP32), immunoblotting(CPP32, and PARP) for SK-pcDNA3 cells(vector only) and SK-Bcl-2 cells(stably expressed bcl-2 gene) were showen to be no significant differences between two cell lines. These results suggested that cell death induced by ethanol was not followed by apoptosis mechanism, and was blocked by the bcl-2 proto-oncogene with moderate ethanol.