• 대한두경부종양학회지
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• 제17권2호
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• pp.139-147
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• 2001

Objectives: The most important differential point of follicular carcinoma from adenoma is capsular invasion or angioinvasion of follicular cells. Serial sections for examination of levels of tumor margins are necessary to watch the invasion. However, the interpretation of capsular invasion or angioinvasion is sometimes not feasible on the routine staining of tumor tissue. The aim of this study is to evaluate the clinical significance of expressions of $p27^{KIP1}$, MIB-1, bcl-2 and p53 in differential diagnosis of follicular adenoma and carcinoma. Materials and Methods: 16 cases of follicular carcinoma and 26 cases of follicular adenoma were entered on study of immunohistochemical stains for $p27^{KIP1}$, MIB-1, bcl-2 and p53. In carcinoma cases, correlation between the above markers, patient's age, tumor size, infiltration pattern and metastasis was studied. Results: $p27^{KIP1}$ labelling index (LI) of follicular carcinoma and adenoma was $4.89{\pm}6.92$ and $14.52{\pm}9.17$, respectively, but there was no significant difference between adenoma and carcinoma (p=0.2560). MIB-1 LI of carcinoma and adenoma was $4.11{\pm}3.89$ and $0.80{\pm}0.75$, respectively, and MIB-1 LI was significantly higher in carcinoma (p=0.0000). bcl-2 expression was seen in 2(12.5%) of 16 carcinoma cases and 130(50.0%) of 26 adenoma cases, and bcl-2 expression rate was higher in adenoma than in carcinoma(p=0.014). In one adenoma and one carcinoma case, p53 expression was noted. In follicular adenoma with atypia compared to adenoma without atypia, lower $p27^{KIP1}$ LI, higher MIB-1 LI and lower bcl-2 expression rate were seen. In follicular carcinoma, MIB-1 LI was significantly higher in invasive carcinoma(p=0.045) and was relatively increased in tumors larger than 3.0cm, showing angioinvasion and distant metastasis. But $p27^{KIP1}$ LI was higher in cases over 40 years old(p=0.008) and with conspicuous capsular invasion. There were no positive correlations between expressions of MIB-1, bcl-2 and p53. Conclusion: MIB-1 labelling index and bcl-2 expression could be helpful for differential diagnosis of follicular adenoma and carcinoma, but p53 showed very low expression rate and no significance in differential diagnosis. $p27^{KIP1}$ labelling index reveals decreasing tendency in carcinoma compared with adenoma, MIB-1 LI was considered as a poor prognostic marker in follicular carcinoma, but $p27^{KIP1}$ LI was higher in carcinoma cases over 40 years old with showing conspicuous capsular invasion. Further study for the significance of $p27^{KIP1}$ labelling index in follicular neoplasms is necessary to evaluate diagnostic value of follicular carcinoma.

• Journal of Chest Surgery
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• 제34권6호
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• pp.447-453
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• 2001

배경: 연부조직 육종의 폐전이의 표준치료법은 폐절제술이지만, 대부분의 폐전이육종은 항암제 투여를 필요로 한다. 항암제 투여는 치료용량에 도달하기전에 발생하는 전신독성으로 인하여 그 효과가 만족스럽지 않다. 연부조직 육종의 항암제로 많이 사용하는 doxorubicin을 폐조직에 직접 투여하면 전신투여시에 비하여 전신독성이 적을 뿐만 아니라 폐에서 10~25배 높은 doxorubicin 농도를 얻을 수 있다. 그러나 이와 같은 고농도 doxorubicin의 암세포에 대한 효과에 대해서는 불명확하다. 대상 및 방법: 본 연구는 methylcholanthrene유도 섬유육종세포주(methylcholanthrene-induced rat fibrosarcoma cell line, MCA 세포)를 여러 농도의 doxorubicin에 24시간 노출한 후 세포독성과 자멸사(apoptosis) 유전자(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) 발현을 살펴보았다. 결과: MCA 세포에 대한 doxorubicin(1-100 $\mu$M)의 세포독성은 용량에 따라서 증가하였으나, 자멸사의 최고치는 5 $\mu$M의 doxorubicin에서 나타났다. 자멸사와 연관된 유전자의 모든 mRNA는 1 $\mu$M에서 대조군에 비해 증가한 후 doxorubicin의 용량이 증가함에 따라 감소하였는데, caspase 8은 5 $\mu$M의 doxorubicin에서도 대조군보다 높은 수치를 보였다. 자멸사와 연관된 단백질은 1 $\mu$M의 doxorubicin에서 가장 높은 수치를 나타낸 후 doxorubicin의 용량이 증가함에 따라 감소하였으나 Bax와 Bcl-xL 단백질은 모든 용량의 doxorubicin에서 대조군과 같거나 높은 수준을 보였다. 결론: 결론적으로 저농도(1-5 $\mu$M)의 doxorubicin에서 자멸사는 MCA세포를 사멸시키는 주된 작용기전이고, 이때에 자멸사와 연관된 유전자 인 Bax, caspase 8, Bcl-xL이 관여되는 것으로 보이며, 그보다 높은 농도의 doxorubicin에서는 자멸사는 억제되지만 MCA 세포에 대한 강력한 세포독성을 보여, 자멸사 이외의 다른 기전이 기여할 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제53권10호
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• pp.898-908
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• 2010

Purpose: The neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism. Methods: The left carotid artery was ligated in 7-day-old Sprague-Dawley (SD) rat pups ($in$ $vivo$ model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation ($in$ $vitro$ model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups. Results: In the $in$ $vivo$ model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the $in$ $vitro$ model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model. Conclusion: rHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2008년도 하계학술대회 논문집 Vol.9
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• pp.169-169
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• 2008

To keep pace with scaling trends of CMOS technologies, high-k metal oxides are to be introduced. Due to their high permittivity, high-k materials can achieve the required capacitance with stacks of higher physical thickness to reduce the leakage current through the scaled gate oxide, which make it become much more promising materials to instead of $SiO_2$. As further studying on high-k, an understanding of the relation between the etch characteristics of high-k dielectric materials and plasma properties is required for the low damaged removal process to match standard processing procedure. There are some reports on the dry etching of different high-k materials in ICP and ECR plasma with various plasma parameters, such as different gas combinations ($Cl_2$, $Cl_2/BCl_3$, $Cl_2$/Ar, $SF_6$/Ar, and $CH_4/H_2$/Ar etc). Understanding of the complex behavior of particles at surfaces requires detailed knowledge of both macroscopic and microscopic processes that take place; also certain processes depend critically on temperature and gas pressure. The choice of $BCl_3$ as the chemically active gas results from the fact that it is widely used for the etching o the materials covered by the native oxides due to the effective extraction of oxygen in the form of $BCl_xO_y$ compounds. In this study, the surface reactions and the etch rate of $Al_2O_3$ films in $BCl_3/Cl_2$/Ar plasma were investigated in an inductively coupled plasma(ICP) reactor in terms of the gas mixing ratio, RF power, DC bias and chamber pressure. The variations of relative volume densities for the particles were measured with optical emission spectroscopy (OES). The surface imagination was measured by AFM and SEM. The chemical states of film was investigated using X-ray photoelectron spectroscopy (XPS), which confirmed the existence of nonvolatile etch byproducts.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2009년도 추계학술대회 논문집
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• pp.67-67
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• 2009

Due to the scaling down of the dielectrics thickness, the leakage currents arising from electron tunneling through the dielectrics has become the major technical barrier. Thus, much works has focused on the development of high k dielectrics in both cases of memories and CMOS fields. Among the high-k materials, $Al_2O_3$ considered as good candidate has been attracting much attentions, which own some good properties as high dielectric constant k value (~9), a high bandgap (~2eV) and elevated crystallization temperature, etc. Due to the easy control of ion energy and flux, low ownership and simple structure of the inductively coupled plasma (ICP), we chose it for high-density plasma in our study. And the $BCl_3$ was included in the gas due to the effective extraction of oxygen in the form of BClxOy compound. In this study, the etch characteristic of ALD deposited $Al_2O_3$ thin film was investigated in $BCl_3/N_2$ plasma. The experiment were performed by comparing etch rates and selectivity of $Al_2O_3$ over $SiO_2$ as functions of the input plasma parameters such as gas mixing ratio, DC-bias voltage and RF power and process pressure. The maximum etch rate was obtained under 15 mTorr process perssure, 700 W RF power, $BCl_3$(6 sccm)/$N_2$(14 sccm) plasma, and the highest etch selectivity was 1.9. We used the x-ray photoelectron spectroscopy (XPS) to investigate the chemical reactions on the etched surface. The Auger electron spectroscopy (AES) was used for elemental analysis of etched surface.

• Journal of Acupuncture Research
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• 제34권3호
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• pp.1-11
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• 2017

Objectives : The purpose of this study was to examine the effects of Acori Graminie Rhizoma Pharmacopuncture (PA-AG) at GV20 on cerebral ischemia-induced dementia in Mice. Methods : Mice were divided into the five following groups: normal, control, acupuncture, PA-AG (17 mg/kg), and PA-AG (34 mg/kg). All groups, except the normal group, had cerebral ischemia induced by occlusion of middle cerebral artery. The control group was not treated. The acupuncture, PA-AG (17 mg/kg), and PA-GA (34 mg/kg) groups were treated every other day with a total of 6 treatments. The effect of treatment was observed by Bax, Bcl-2, Bax/Bcl-2 ratio, cytochrome c, cresyl violet, and choline acetyltransferase staining. Results : In the PA-AG (34 mg/kg) group, the intensity of Bax was decreased and the intensity of Bcl-2 was increased. The Bax/Bcl-2 ratio also decreased in the PA-AG (34 mg/kg) group. The intensity of cytochrome c protein stain was decreased in the PA-AG (17 mg/kg) group. The density of neurons stained by cresyl violet and choline acetyltransferase (ChAT) was increased in the AT, PA-AG (17 mg/kg), and PA-AG (34 mg/kg) groups when compared with that of the control group. Conclusion : PA-AG at GV20 was effective on cerebral ischemia-induced dementia in mice.

• Clinical and Experimental Reproductive Medicine
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• 제30권1호
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• pp.77-84
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• 2003

Objective : The aim of this study was to evaluate the influence of three different media on preimplatation embryo development and the expression of Bcl-2, Mcl-1, Bax, and Bok in mouse. Materials and Methods: Two-cell embryos were retrieved from ICR female mice (4 weeks old) at 48 hr after hCG injection and cultured in Ham's F-10, HTF, and G1.2 media. The developmental rate of 2-cell embryos was evaluated from 24 hr to 72 hr after culture. RT-PCR was performed for the detection of Bcl-2, Mcl-1, Bax, and Bok gene expression. Results: The rates of morula and blastocyst in HTF and G1.2 media (88%, 98.1%) were significantly higher than those in Ham's F-10 media (39.6%) at 48 hr. Likewise, the rates of hatching and hatched blastocyst in HTF and G1.2 media (21.9%, 52.9%) were higher than those in Ham's F-10 media (3.5%) at 72 hr. Bcl-2 and Bax mRNAs were highly detected in embryos cultured in Ham's F-10 when compared in embryos cultured in HTF and G1.2. In contrast, the expression of Mcl-1 and Bok was not significantly different. Conclusion: These results show that HTF and G1.2 culture media increase the rate of blastocyst formation and stimulate Bcl-2 and Bax gene expression in mouse preimplantation embryos.

• 대한수의학회지
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• 제45권1호
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• pp.17-23
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• 2005

In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)-${\alpha}$ on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells ($1{\times}10^{6}$/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached $100mm^3$, mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN-${\alpha}$, or arsenic trioxide and IFN-${\alpha}$. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-${\alpha}$. In arsenic trioxide and IFN-${\alpha}$ treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days. Also, positive signals of Bax and Bad were increased at 48 to 96 hr and decreased at 8 day. Whereas, positive cells of Bcl-2 were steadily decreased at 12 to 48 hr and restored to the background level at 8 days. Our data showed that immunoreactivity of Bcl-2 was decreased at 12 to 48 hr, while positive signals of Bax and Bad were increased in accordance with apoptotic index at these times. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN-${\alpha}$ significantly inhibited the growth of LL2 tumor cells and induced apoptosis through the up and down-regulation of Bcl-2 gene family.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권6호
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• pp.617-624
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• 2007

Insulin-like growth factor(IGF) is the most abundant growth factor in bone matrix. Recent studies have shown that it can sensitize apoptotic cell death of osteoblasts. Thus, this study investigated whether IGF-II aggravates irradiation-induced cell death of osteoblasts. Cultured MC3T3 osteoblasts were irradiated and IGF-II was added at the concentration of 50 ng/ml immediately after the irradiation. Cell viability was measured by MTT assay. Changes in cell death and cell cycle were analyzed by flow cytometry. The expression of proapoptotic gene bax and antiapoptotic gene bcl-2 was quantified by real time RT-PCR and Western blot. A dose of 30 Gy caused G2/M arrest and increased cell death through both necrosis and apoptosis, while irradiation from 4 to 10 Gy little affected cell cycle and death. IGF-II treatment reduced cell viability without stimulating cell proliferation and changing cell cycle. Combined treatment of IGF-II with irradiation decreased cell viability and proliferation and increased cell death along with G2/M arrest. These effects were not different from those of irradiation only. At transcriptional and protein levels, IGF-II treatment did not affect bax and bcl-2 expression, whereas irradiation increased the expression ofbax without changes in bcl-2. IGF-II in combination with irradiation showed similar findings. These results suggest that IGF-II could modulate apoptotic cell death through mechanisms other than an imbalance between bax and bcl-2 gene expression, although its effect was overridden by irradiation.

• Molecules and Cells
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• 제38권3호
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• pp.279-284
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• 2015

Obatoclax, a pan-Bcl2 inhibitor, shows antitumor activities in various solid malignancies. Bcl2-deficient mice have shown the importance of Bcl2 in osteoclasts, as the bone mass of the mice was increased by the induced apoptosis of osteoclasts. Despite the importance of Bcl2, the effects of obatoclax on the proliferation and differentiation of osteoclast precursors have not been studied extensively. Here, we describe the anti-proliferative effects of obatoclax on osteoclast precursors and its negative role on fusion of the cells. Stimulation with low doses of obatoclax significantly suppressed the proliferation of osteoclast precursors in a dose-dependent manner while the apoptosis was markedly increased. Its stimulation was sufficient to block the activation of ERK MAP kinase by RANKL. The same was true when PD98059, an ERK inhibitor, was administered to osteoclast precursors. The activation of JNK1/2 and p38 MAP kinase, necessary for osteoclast differentiation, by RANKL was not affected by obatoclax. Interestingly, whereas the number of TRAP-positive mononuclear cells was increased by both obatoclax and PD98059, fused, multinucleated cells larger than $100{\pm}m$ in diameter containing more than 20 nuclei were completely reduced. Consistently, obatoclax failed to regulate the expression of osteoclast marker genes, including c-Fos, TRAP, RANK and CtsK. Instead, the expression of DC-STAMP and Atp6v0d2, genes that regulate osteoclast fusion, by RANKL was significantly abrogated by both obatoclax and PD98059. Taken together, these results suggest that obatoclax down-regulates the proliferation and fusion of osteoclast precursors through the inhibition of the ERK1/2 MAP kinase pathway.