• Journal of Korean Neurosurgical Society
• /
• 제63권4호
• /
• pp.444-454
• /
• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

• Molecules and Cells
• /
• 제21권3호
• /
• pp.367-375
• /
• 2006

We previously identified a novel cancer/testis antigen gene CAGE by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera of gastric cancer patients. CAGE is expressed in many cancers and cancer cell lines, but not in normal tissues apart from the testis. In the present study, we investigated its role in the motility of cells of two human cancer cell lines: HeLa and the human hepatic cancer cell line, SNU387. Induction of CAGE by tetracycline or transient transfection enhanced the migration and invasiveness of HeLa cells, but not the adhesiveness of either cell line. Overexpression of CAGE led to activation of ERK and p38 MAPK but not Akt, and inhibition of ERK by PD98059 or p38 MAPK by SB203580 counteracted the CAGE-promoted increase in motility in both cell lines. Overexpression of CAGE also resulted in a reduction of ROS and an increase of ROS scavenging, associated with induction of catalase activity. Inhibition of ERK and p38 MAPK increased ROS levels in cells transfected with CAGE, suggesting that ROS reduce the motility of both cell lines. Inhibition of ERK and p38 MAPK reduced the induction of catalase activity resulting from overexpression of CAGE, and inhibition of catalase reduced CAGE-promoted motility. We conclude that CAGE enhances the motility of cancer cells by activating ERK and p38 MAPK, inducing catalase activity, and reducing ROS levels.

• Journal of Chest Surgery
• /
• 제44권2호
• /
• pp.142-147
• /
• 2011

Background: Endovascular aortic aneurysm repair (EVAR) has come into use and been widely extended because of the low complication rate and less-invasiveness. This article aimed to describe our experience in the treatment of abdominal aortic aneurysm with EVAR. Materials and Methods: A retrospective review was conducted for the 22 patients who underwent EVAR in a single hospital December 2001 to June 2009. Results: The mean age of the patients was $68.5{\pm}7.6$ years. There were several risk factors and comorbidities in 20 patients (90.9%). The mean diameter of the aortic aneurysms was $61.2{\pm}12.9$ mm. The mean length, diameter, and angle of the aneurysmal neck were $30.5{\pm}15.5$ mm, $24.0{\pm}4.5$ mm, and $43.9{\pm}16.0^{\circ}$, respectively. The mean follow-up period of the patients was $28.8{\pm}29.5$ months. The 30-day postoperative mortality was none. Seven patients (31.8%) had endoleaks during the hospital stay and three patients (13.6%) had endoleaks during the follow-up period. One patient (4.5%) died due to a ruptured aortic aneurysm. The cumulative patient survival rates were 88.2%, 88.2%, and 70.6% at 1, 3, and 5 years of follow-up, respectively. Conclusion: EVAR is currently a safe, feasible procedure for high risk patients with abdominal aortic aneurysm because of low postoperative complication and mortality if patients are selected properly and followed up carefully.

• 한국진공학회:학술대회논문집
• /
• 한국진공학회 2012년도 제42회 동계 정기 학술대회 초록집
• /
• pp.523-523
• /
• 2012

As the wafer geometric requirements continuously complicated and minutes in tens of nanometers, the expectation of real-time add-on sensors for in-situ plasma process monitoring is rapidly increasing. Various industry applications, utilizing plasma impedance monitor (PIM) and optical emission spectroscopy (OES), on etch end point detection, etch chemistry investigation, health monitoring, fault detection and classification, and advanced process control are good examples. However, process monitoring in semiconductor manufacturing industry requires non-invasiveness. The hypothesis behind the optical monitoring of plasma induced ion current is for the monitoring of plasma induced charging damage in non-invasive optical way. In plasma dielectric via etching, the bombardment of reactive ions on exposed conductor patterns may induce electrical current. Induced electrical charge can further flow down to device level, and accumulated charges in the consecutive plasma processes during back-end metallization can create plasma induced charging damage to shift the threshold voltage of device. As a preliminary research for the hypothesis, we performed two phases experiment to measure the plasma induced current in etch environmental condition. We fabricated electrical test circuits to convert induced current to flickering frequency of LED output, and the flickering frequency was measured by high speed optical plasma monitoring system (OPMS) in 10 kHz. Current-frequency calibration was done in offline by applying stepwise current increase while LED flickering was measured. Once the performance of the test circuits was evaluated, a metal pad for collecting ion bombardment during plasma etch condition was placed inside etch chamber, and the LED output frequency was measured in real-time. It was successful to acquire high speed optical emission data acquisition in 10 kHz. Offline measurement with the test circuitry was satisfactory, and we are continuously investigating the potential of real-time in-situ plasma induce current measurement via OPMS.

• KSBB Journal
• /
• 제18권6호
• /
• pp.485-489
• /
• 2003

HGF는 내피세포의 증식 및 이동을 일으키는 강력한 혈관 신생 유도인자 및 생존인자로서 작용한다고 알려져 있다. 본 연구에서는 HUVECs 세포를 이용하여 내피세포의 이동 및 단백질분해효소의 분비에 미치는 HGF의 효과를 확인하였다. 그 곁과, HGF 처리 (10ng/$m\ell$)에 의해 HUVECs 세포의 이동이 약 3.3배 촉진되어, HGF가 HUVECs 세포에서 강력한 이동 유도인자라는 사실을 확인하였다. 내피세포의 이동에 관여할 것이라 여겨지는 MMPs, TIMPs 및 플라스민의 분비에 미치는 HGF의 효과를 관찰한 결과, HGF에 의해 MMP-2 및 MMP-3의 분비양이 각각 3.3배와 6.1배씩 증가되었다. HGF에 의한 TIMPs 분비효과를 관찰한 결과, TIMP-1은 대조군에 비해 약 1.8배 분비가 증가되었으나, TIMP-2는 대조군에 비해 약 3.1배 분비가 억제되었다. 또한, 광범위 MMPs-억제제인 BB-94 (20ng/$m\ell$) 및 플라스민 억제제인 $\alpha$$_2$-antiplasmin (100mU)을 처리했을 때, HGF에 의해 유도된 혈관내피세포의 이동이 거의 완벽하게 억제되었다. 결론적으로, HGF는 HUVECs 세포에서 MMP-2, MMP-3, MMP-9, TIMP-1 및 플라스민의 분비 증가를 일으켰으며, HGF에 의해 분비가 증가 된 단백질분해효소에 의해 세포외기질 및 기저막 단백질로의 혈관내피세포의 이동이 촉진되고, 결과적으로 혈관신생을 유도할 것이라 사료된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제28권2호
• /
• pp.155-160
• /
• 2002

Oral squamous cell carcinoma (OSCC), the most common head and neck cancer, shows poor prognosis as a result of frequent local invasion and lymph node metastasis that is mediated by multiple proteolytic enzymes and angiogenesis. In recent reports, angiogenesis is known to play an important role in tumor invasion and metastasis. The purpose of this study was to determine the role of angiogenesis in OSCCs, particularly with respect to the invasive and the metastatic potential. The microvessel density (CD31) in 34 human OSCC cases were investigated by immunohistochemistry, and reviewed with respect to the invasiveness and the presence of lymph node metastasis and following results were obtained. The blood vessel density $(28.8{\pm}7.9)$ in the strong invasive cases were significantly higher than those $(23.3{\pm}6.9)$ in the weak invasive cases. (p<0.05) In the 14 cases with lymph node metastasis, the average blood vessel density was $28.5{\pm}9.6$. On the other hand, in the 20 cases without lymph node metastasis, the blood vessel density was $25.2{\pm}6.4$. The blood vessel density was not statistically related to lymph node metastasis. (p>0.05) These results suggest that angiogenesis may be related to the local invasion of OSCC and further research will be needed to investigate the possibility that antiangiogenic agent can be used as an anticancer agent for OSCC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제31권1호
• /
• pp.1-6
• /
• 2005

It becomes more concerned that the cell adhesion molecule plays an important role in the process of malignant transformation and tumor behaviors including invasive growth and metastasis. It is postulated if the expression of adhesion molecule is reduced in tumor tissue, the tumor cell will be undifferentiated and lose their cell adhesion ability and polarity. So the tumor cells lost the adhesion of cell to cell and to basement membrane that they became more aggressive. Reduced cadherin expression enhances invasiveness through infiltrative growth and metastasis of tumor cells is well known and mostly accepted in many epithelia tumors. We explored the expression of E-cadherin by immunohistochemical staining in 50 oral squamous cell carcinomas and investigated the correlation between the expression of E-cadherin and clinicopathologic parameters and prognosis. The expression of E-cadherin was reduced in 40/50(80%) of primary tumors, and 21/22(95.5%) of lymph nodes. The reduced expression of the E-cadherin was associated with lymph node metastasis(P=0.029), invasive mode(P=0.030) and marginal status(P=0.038). Survival analysis showed that predictive period of E-cadherin reduced group(37 months) was lower than that of E-cadherin preserved group(60 months), but there was no statistical significant difference.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제33권2호
• /
• pp.103-108
• /
• 2007

Cyclooxygenase-2 (Cox-2) is known as one of the critical factor in carcinomas of various organs. However, the importance of Cox-2 in oral squamous cell carcinoma has not been fully described yet. The purpose of this study is to evaluate the anti-cancer effect of selective cox-2 inhibitor, celecoxib in an oral squamous cell carcinoma cell line, KB with respect to cytotoxicity test, in vitro invasion and MMP-2 expression. In cytotoxicity test, celecoxib treated group showed definitely concentration dependent cytotoxicity. In addition, administration of celecoxib reduced the invasive potential of KB cell line significantly in invasion assay. However, there was no remarkable difference of the MMP-2 expression between the celecoxib treated group and the control group. Considering these data, celecoxib had a potential cytotoxic agent to oral squamous cell carcinoma cells. Also, it had anti-invasive property without acting on the MMP-2 expression mechanism. Therefore, it was postulated that celecoxib had the possibility of anti-cancer agent in treatment strategies of oral squamous cell carcinoma.

• Clinical and Experimental Reproductive Medicine
• /
• 제45권1호
• /
• pp.10-16
• /
• 2018

Objective: Placental oxidative stress is known to be a factor that contributes to pregnancy failure. The aim of this study was to determine whether selenium could induce antioxidant gene expression and regulate invasive activity and mitochondrial activity in trophoblasts, which are a major cell type of the placenta. Methods: To understand the effects of selenium on trophoblast cells exposed to hypoxia, the viability and invasive activity of trophoblasts were analyzed. The expression of antioxidant enzymes was assessed by reverse-transcription polymerase chain reaction. In addition, the effects of selenium treatment on mitochondrial activity were evaluated in terms of adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species levels. Results: Selenium showed positive effects on the viability and migration activity of trophoblast cells when exposed to hypoxia. Interestingly, the increased heme oxygenase 1 expression under hypoxic conditions was decreased by selenium treatment, whereas superoxide dismutase expression was increased in trophoblast cells by selenium treatment for 72 hours, regardless of hypoxia. Selenium-treated trophoblast cells showed increased mitochondrial membrane potential and decreased reactive oxygen species levels under hypoxic conditions for 72 hours. Conclusion: These results will be used as basic data for understanding the mechanism of how trophoblast cells respond to oxidative stress and how selenium promotes the upregulation of related genes and improves the survival rate and invasive ability of trophoblasts through regulating mitochondrial activity. These results suggest that selenium may be used in reproductive medicine for purposes including infertility treatment.

• Molecules and Cells
• /
• 제39권3호
• /
• pp.258-265
• /
• 2016

In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.