• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1783-1789
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• 2014

Background: The EMSY gene encodes a BRCA2-binding partner protein that represses the DNA repair function of BRCA2 in non-hereditary breast cancer. Although amplification of EMSY gene has been proposed to have prognostic value in breast cancer, no data have been available concerning EMSY tissue expression patterns and its associations with clinicopathological features. Materials and Methods: In the current study, we examined the expression and localization pattern of EMSY protein by immunohistochemistry and assessed its prognostic value in a well-characterized series of 116 unselected breast carcinomas with a mean follow up of 47 months using tissue microarray technique. Results: Immunohistochemical expression of EMSY protein was detected in 76% of primary breast tumors, localized in nuclear (18%), cytoplasmic (35%) or both cytoplasmic and nuclear sites (23%). Univariate analysis revealed a significant positive association between EMSY expression and lymph node metastasis (p value=0.045) and larger tumor size (p value=0.027), as well as a non-significant relation with increased risk of recurrence (p value=0.088), whereas no association with patients' survival (log rank test, p value=0.482), tumor grade or type was observed. Conclusions: Herein, we demonstrated for the first time the immunostaining pattern of EMSY protein in breast tumors. Our data imply that EMSY protein may have impact on clinicipathological parameters and could be considered as a potential target for breast cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8847-8853
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• 2014

The aim of this study was to establish the expression and localization of E-cadherin and ${\beta}$-catenin in oral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevant histopathological variables. E-cadherin and ${\beta}$-catenin expression in normal oral epithelia and in oral squamous cell carcinomas was examined immunohistochemically, and associations with histopathological differentiation and prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiated and (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade (p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, with no correlation to the histological grade (p=0.106). ${\beta}$-Catenin expression was found in 87% of the squamous cells of well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expression was significantly associated with histological grade (p=0.000). the nuclear ${\beta}$-Catenin expression appeared in 3.3% of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells ${\beta}$-Catenin localized in the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression of ${\beta}$-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closely linked to ${\beta}$-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structural association and the role of both in tumor progression.

• Journal of Korean Neurosurgical Society
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• 제46권4호
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• pp.333-339
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• 2009

Objective : Few studies on the clinical spectrum of automated pressure-controlled discography (APCD)-defined positive discs have been reported to date. Thus, the present study was undertaken to analyze clinical parameters critical for diagnosis of discogenic pain and to correlate imaging findings with intradiscal pressures and pain responses in patients with APCD-positive discs. Methods : Twenty-three patients who showed APCD-positive discs were selected for analysis. CT discogram findings and the degrees of nuclear degeneration seen on MRI were analyzed in comparison to changes of intradiscal pressure that provoked pain responses; and clinical pain patterns and dynamic factors were evaluated in relation to pain provocation. Results : Low back pain (LBP), usually centralized, with diffuse leg pain was the most frequently reported pattern of pain in these patients. Overall, LBP was most commonly induced by sitting posture, however, standing was highly correlated with L5/S1 disc lesions (p<0.01). MRI abnormalities were statistically correlated with grading of CT discogram results (p<005); with most pain response observed in CT discogram Grades 3 and 4. Pain-provoking pressure was not statistically correlated with MRI grading. However, it was higher in Grade 3 than Grade 4. Conclusion : APCD-positive discs were demonstrated in patients reporting centralized low back pain with diffuse leg pain, aggravated by sitting and standing. MRI was helpful to assess the degree of nuclear degeneration, yet it could not guarantee exact localization of the painful discs. APCD was considered to be more useful than conventional discography for diagnosis of discogenic pain.

• 대한핵의학회지
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• 제26권2호
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• pp.244-250
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• 1992

Both interictal and ictal $^{99m}Tc-HMPAO$ brain SPECT were performed in 22 patients with medically intractable epilepsy. Localization of epileptic foci in our patients was made by combined results of EEG and other tests, including Wada test, magnetic resonance imaging, and neuropsychometric test. Among them, ictal $^{99m}Tc-HMPAO$ SPECT, localized epilptic foci in 20 of 22 patients and provided evidence of epileptic focus in 12 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci during the ictal study with decreased rCP in interictal study. Ictal $^{99m}Tc-HMPAO$ SPECT was particularly useful for investigating epileptic foci, and when correlated with simultaneously recorded ictal EEG, provided further insight for localizing epileptic foci. Conclusively, $^{99m}Tc-HMPAO$ SPECT is. a useful, noninvasive method of localizing epileptic activity which may be particularly important for presurgical investigations, especially in those patients without large morphological lesions.

• 대한핵의학회지
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• 제27권1호
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• pp.65-70
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• 1993

Among 64 patients with acute myocardial infarction who underwent coronary angiogrphy, 7 patients (10.9%) showed normal coronary artery. Six patients were men and 1 patient was female. The mean age of patients were $31.1{\pm}3.9$ years. Among the risk factors of coronary heart disease, smoking was most probable factor in patients with acute myocardial infarction with normal coronary angiography. $^{99m}Tc$-MIBI heart SPECT performed 5 of 7 patients and showed that it could be used in diagnosis, localization, extent of infarct area in patients with acute myocardial infarction with normal coronary angiograpy. But follow up $^{99m}Tc$-MIBI heart SPECT study will be needed to define the ability of myocardial viability in this patients.

• Journal of Ginseng Research
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• 제45권6호
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• pp.734-743
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• 2021

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer. Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess total and gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR, dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependent manner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cells and enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancer cells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundance significantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation and growth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression. Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.178-184
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• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• Tuberculosis and Respiratory Diseases
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• 제46권2호
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• pp.185-194
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• 1999

연구배경: NF-$\kappa$B는 단백질이 생성된 후의 변형(post-translational modification)과 세포내에서의 위치 변화(subcellular localization)에 따라 그 작용이 결정되는 특성을 가진 전사 인자로서 최초에는 면역반응에 있어 중요한 역할을 하는 사실이 알려졌으나 그후 이러한 작용이외에도 급성기 염증 반응, 바이러스의 증식, 세포의 발생과 분화에 있어 중요한 작용을 한다는 사실이 알려지게 되었다. 최근의 연구들에서 NF-$\kappa$B 전사 인자가 정상 세포로부터 암세포로의 형질전환에 있어서도 어떤 기능을 할 것이라는 사실들이 알려지게 되었다. NF-$\kappa$B가 암세포로의 형질 전환, 나아가 암세포의 생성에 어떤 역할을 제공한다면 이러한 사실은 나아가 향후의 암치료에 있어서도 유용한 지식이 될 수 있다. NF-$\kappa$B 전사 인자가 인체 암세포에 있어서 세포의 형질 변환에 연관될 수 있다는 사실은 몇몇 암종에서 알려져 있으나 폐암에서의 NF-$\kappa$B 전사 인자의 종양 생성기능에 있어서는 아직 연구된 바가 없다. 방 법: 본 연구에서는 배양된 인체 폐암세포주에 있어서 NF-$\kappa$B family 전사 인자들의 발현정도를 western blot를 이용하여 관찰하고 과발현된 NF-$\kappa$B 전사 인자의 세포내 위치가 세포핵인지 세포질내에 존재하는 것인지를 각각의 단백질 분획에서 western blot를 시행하여 관찰하였고 또한 immunocy-tochemistry를 시행하여 그 발현 양상을 확인하였다. 존재하는 NF-$\kappa$B 전사 인자가 어떠한 복합체의 형태인지를 알아보기 위하여 세포주의 단백 추출물에서 NF-$\kappa$B family 전사 인자에 대한 항체를 사용하여 immunoprecipitation을 시행하였다. 세포주 단백추출물의 $\kappa$B consensus oligonucleotide에의 결합여부를 보기위하여 electrophoretic mobility shift assay를 시행하였다. 결 과: 배양된 인체 폐암세포주에서는 NF-$\kappa$B family의 p50 subunit, p65 subunit가 발현되어 있었고 p50 subunit의 발현은 세포핵내에 국한하여 위치하고 있음을 western blot와 immunocytochemistry를 통하여 관찰할 수 있었다 immunoprecipitation assay는 세포내에서 p50 subunit가 p65 subunit와 복합체를 이루는 상태로 존재하고 있음을 보여주었다. 폐암세포주의 세포핵 추출물은 NF-$\kappa$B consensus oligonucleotide와 결합할 수 있음을 electrophoretic mobility shift assay를 통하여 확인할 수 있었다. 결 론: 인체 폐암세포주에서 NF-$\kappa$B family 전사 인자의 발현이 활성화되어 있으며 NF-$\kappa$B family 전사 영자가 인체 폐암 형성에 있어 어떤 역할을 할 가능성을 시사한다.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2304-2310
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• 2014

The synthesis and in vivo evaluation of 5-methoxy-2-(phenylethynyl)quinoline (MPEQ) 3 as a potential mGluR5 selective radioligand is described. We have identified MPEQ 3 exhibiting the analgesic effect in the neuropathic pain animal model. The effect of mGluR5 on neuronal activity in rat brain was evaluated through FDG/PET imaging in the presence of MPEQ 3. In addition, the PET study of [$^{11}C$]MPEQ 3 proved that accumulation of [$^{11}C$]MPEQ 3 in rat brain was correlated to the localization of the mGluR5.

• 핵의학기술
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• 제19권2호
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• pp.74-80
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• 2015

유방 림프절 검사는 유방암이 있는 환자들에게 외과적 수술 전 후에 검사가 시행되고, 악성 종양의 림프절 전이를 조기에 진단할 수 있는 검사방법으로 검사 시 체표윤곽을 정확하게 나타내는 것이 중요하다. 현재 대부분 병원에서 $^{99m}Tc$ 점선원 또는 $^{57}Co$ 면선원을 이용한 방법을 사용하고 있다. 따라서 본 논문에서는 위의 두 가지 방법 외에 $10m{\ell}$ 주사기를 이용하는 방법, 산란선 광자에너지를 이용한 방법, SPECT/CT에서 scout촬영을 이용한 방법을 추가하여 영상에서 위치 정보를 유용하게 제공하는 방법과 피폭선량을 비교 및 평가하고자 한다. Rando phantom과 SYMBIA T16 장비를 사용하였으며 Phantom의 우측 13번째에 0.11 MBq의 점선원을 삽입하여 종양을 만들었고, 우측 유방 위치에 37 MBq의 점선원으로 주사 부위를 만들었다. 첫 번째 방법은 $^{99m}Tc$ 점선원으로 Phantom의 체표윤곽을 30초 동안 그려 영상을 획득하는 방법이며, 두 번째는 $^{57}Co$ 면선원을 환자의 후면부와 좌측면에 위치하여 30초 동안 체표윤곽을 얻는 방법이며, 세 번째는 $^{99m}TcO_4$ 37 MBq와 생리식염수로 채운 $10m{\ell}$ 주사기를 이용한 방법이다. 그리고 네 번째는 선원 없이 $^{99m}Tc$의 에너지와 scatter의 광자 에너지를 이용한 방법이며, 마지막은 SPECT/CT의 scout영상과 유방 영상을 전선화 코드를 이용하여 융합하는 방법이다. 이때 전면 영상과 우측 영상을 각각 3분씩 얻었으며 검사 시 개인피폭 선량계(ECOTEST, DKG-21)를 사용하여 피폭선량을 계측하였다. 각각의 영상을 종양 대 배후 방사능 비(TBR)와 피폭선량을 비교 및 분석하였으며 다섯 가지 방법의 영상을 방사선사와 핵의학 전공의에게 설문조사를 하여 선호도를 파악하였다. 첫 번째 방법에서의 종양 대 배후 방사능 비의 값은 전면 영상은 334.9, 우측 영상은 117.2이며 피폭선량은 $2{\mu}\;Sy$가 계측되었고, 두 번째 방법에서는 각각 266.1, 124.4, $2{\mu}\;Sy$로 평가되었고, 세 번째 방법에서는 117.4, 99.6, $2{\mu}\;Sy$로 평가되었으며 네 번째 방법에서는 3.2, 7.6이며 $0{\mu}\;Sy$로 평가되었다. 그리고 마지막 방법에서의 565.6, 141.8, $30{\mu}\;Sy$로 평가되었다. TBR값은 마지막 방법이 가장 높았고 네 번째 방법이 가장 낮았다. 또한 피폭선량은 마지막 방법이 가장 높았으며 네 번째 방법이 가장 낮았다. 그리고 설문 조사 결과는 마지막 방법이 가장 좋은 점수가 나왔고 네 번째 방법이 가장 낮은 점수가 나왔다. 유방 림프절 검사는 유방암이 있는 환자들에게 검사 시 종양의 위치를 정확하게 영상화하는 것이 중요하다. 실험 결과 SPECT/CT의 scout 촬영을 이용한 검사 방법은 종양 대 배후 방사능 비의 값이 가장 좋고 설문 조사 결과에서도 가장 좋은 점수를 얻어 영상에서 환자의 위치 정보를 유용하게 제공해주는 방법으로 평가되었다. 그러나 피폭 선량은 SPECT/CT의 scout 촬영 시 다른 검사방법보다 많이 나왔으나 일반인의 연간 피폭선량한도인 1 mSy를 기준으로 비교하면 피폭량은 미미하다고 할 수 있다. Scout촬영 시 80 kV이하로 검사가 가능하다면 피폭선량도 줄이고 환자의 위치 정보를 유용하게 영상화 할 수 있는 방법이 될 수 있을 것이다.