• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3311-3317
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• 2014

Background: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDI${\alpha}$) activity on migration and invasion of estrogen receptor positive ($ER^+$) and negative ($ER^-$) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDI${\alpha}$ and other proteins interacting directly or indirectly with RhoGDI${\alpha}$ in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. Materials and Methods: $ER^+$ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDI${\alpha}$ using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDI${\alpha}$. Results: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDI${\alpha}$ in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDI${\alpha}$ in MCF7, while only one protein was identified in the upregulation of RhoGDI${\alpha}$ in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-${\alpha}$ activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Conclusions: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDI${\alpha}$ with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2291-2295
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• 2014

Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group ($12.1-15.4{\pm}3.8%$) was significantly higher than those of pcDNA3.1-NS ($7.2-12.0{\pm}1.7%$) and non-transfection groups ($4.1-6.5{\pm}1.8%$, P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS down-regulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.1961-1970
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• 2014

Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.179-183
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• 2016

Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes.

• 대한두경부종양학회지
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• 제33권1호
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• pp.21-29
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• 2017

Methylation of CpG islands in the promoter region of genes acts as a significant mechanism of epigenetic gene silencing in head and neck squamous cell carcinoma (HNSCC). DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable mark. In the present study, we assessed the genome-wide preliminary screening and were to identify novel methylation biomarker candidate in HNSCC. Genome-wide methylation analysis was performed on 10 HNSCC tumors using the Methylated DNA Isolation Assay (MeDIA) CpG island microarray. Validation was done using immunohistochemistry using tissue microarray of 135 independent HNSCC tumors. In addition, in vitro proliferation, migration/invasion assays, RT-PCR and immunoblotting were performed to elucidate molecular regulating mechanisms. Our preliminary validation using CpG microarray data set, immunohisto-chemistry for HNSCC tumor tissues and in vitro functional assays revealed that methylation of the Homeobox B5 (HOXB5) and H6 Family Homeobox 2 (HMX2) could be possible novel methylation biomarkers in HNSCC.

• Journal of Korean Neurosurgical Society
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• 제47권1호
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• pp.11-16
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• 2010

Objective: Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma. Methods: Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcription-quantitative PCR analysis (RT-PCR) and immunohistochemical analysis. Results: Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed. Conclusion: Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.

• 한국응용곤충학회지
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• 제57권4호
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• pp.323-328
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• 2018

외래침입종이 자생종에 미치는 잠재적인 영향에 관하여 세계적인 관심이 증가하고 있음에도 그러한 침입의 결과들은 여전히 부족한 실정이다. 유럽좁쌀바구미(cabbage seedpod weevil, CSPW, Ceutorhynchus obstrictus)는 1990년대 초에 한반도에 침입하였다. 침입 후 20여 년 동안 관찰과 2010년 이후 중점적인 조사를 통해 유채 꽃에서 침입종인 유럽좁쌀바구미가 가장 우점을 이루고 있으며, 제주도와 울릉도를 포함한 남한 전역으로 확산되어 있다. 그의 확산은 자생종인 유채좁쌀바구미(rapseed weevil, RSW, C. albosuturalis)의 냉이 등 십자화과 잡초로 서식처 후퇴가 맞물려 일어나고 있다. 한편, 한반도와 제주도 사이에 위치한 여서도는 현재 그들의 비율이 약 1:1로 나타나고 있어 이 섬에는 유럽좁쌀바구미가 최근에 유입된 것으로 보인다. 자생종의 생태적 지위(ecological niche)가 외래침입종으로 대체되는 근본적인 기작은 확실하게 알 수 없지만, 자원경쟁(exploitative competition)의 잠재적인 역할을 배제할 수는 없을 것이다. 자연생태계 내에서 외래침입종이 자생종을 신속하게 대체하고 있음을 확인한 이 결과는 앞으로 또 다른 외래종의 침입 방지 노력을 요구하고 있다.

• 한국융합학회논문지
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• 제13권5호
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• pp.295-305
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• 2022

이 연구는 중·고등 학생선수를 대상으로 인권침해 피해 경험에 영향을 미치는 요인의 인권침해 발생 메커니즘을 분석하여 인권침해를 줄일 수 있는 현실적인 정책적 방향 제시를 목적에 둔다. 이를 위해 구조화된 설문을 통해 수집된 학생선수 13,205명의 응답 자료를 로지스틱 회귀분석을 활용하여 분석하였다. 독립변인은 팀 분위기, 소속 종목 인권의식, 체육계 인권의식 등, 종속변인은 성적폭력, 성적 수치심, 신체 폭력, 언어폭력, 따돌림, 사생활 및 학습권 침해, 운동 관련 공정하지 않은 지도자의 행동 등으로 구성하였다. 분석 결과 첫째, 팀 분위기, 소속 종목 인권의식, 체육계 인권의식은 신체 폭력, 언어폭력, 따돌림, 사생활 및 학습권 침해 피해에 유의미한 영향을 미치는 요인으로 나타났다. 둘째, 성적폭력 경험에 대해서는 팀 분위기, 체육계 인권침해 의식 수준 변수는 유의미한 영향을 미쳤으나 체육계 폭력허용도, 소속 종목 인권의식은 의미 있는 변수로 나타나지 않았다. 셋째, 운동 관련 불공정 경험은 팀 분위기, 체육계 전반적인 폭력허용도 수준, 체육계 인권침해 의식 수준이 유의미한 영향을 미치는 것으로 나타났다.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.53-63
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• 2024

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 ㎍/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0±3.0%, and 48.0±2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

• 한국식품위생안전성학회지
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• 제39권3호
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• pp.181-190
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• 2024

소 유방염 관련 대장균(BMEC)은 생산되는 우유의 양과 품질을 변화시키고 도태율을 높임으로써 전 세계 낙농 산업에 심각한 재정적 손실을 초래할 수 있는 주요 원인 물질로 간주된다. 연구자, 수의사, 농부가 가장 효과적인 치료법과 진단 기술을 이해하고 결정하는 것은 젖소 유방염을 극복하는데 중요하다. 특히 무증상 혹은 준임상형 유방염의 경우, 소는 뚜렷한 증상을 보이지 않고, 장기간에 걸쳐 겉보기에 정상적인 우유를 계속 분비하여 원인 병원체인 대장균이 무리 내에서 감염을 퍼뜨릴 수 있다. 유방염 예방을 위해서는, 병원균의 유방 내 침입, 감염 확립, 유방의 염증의 3단계 병인 과정에 대한 이해가 필수적이다. 지금까지 대장균 유방염의 임상적 중증도에 기여하는 독성 인자와 병원성 사이에 명확한 상관관계가 발견되지 않았다. 다제내성 대장균과 새로운 내성 기전의 진화는 유방염 치료에 항생제를 광범위하게 사용하고 있기 때문에 문제시 되고 있는 실정이다. 따라서 BMEC 치료의 효능을 향상시키기 위해서는 대체제 발굴이 중요하다. 지난 30년 동안 소 유방염의 역학 조사를 위해 다양한 유전자형 분석 기술이 사용되었다. 이러한 연구는 BMEC 계통 간의 진화 관련성 뿐 아니라 기원, 전염 경로, 개체군 구조에 대한 이해를 크게 향상시켰다. 따라서 본 리뷰에서는 BMEC의 전반적 개요를 제공하여 병인, 유전적 관계, 발병 기전, 관리 및 질병 통제를 위한 새로운 치료 옵션에 대한 통찰력을 제공하고자 한다.