• 제목/요약/키워드: molecular therapy

검색결과 1,053건 처리시간 0.028초

Association between Genetic Polymorphism of Peroxisome Proliferator-Activated Receptor Alpha Leu162Val and Metabolioc Syndrome in Korean (한국인에서 peroxisome proliferator-activated receptor alpha Leu162Val 유전자 다형성과 대사증후군간의 관련성)

  • Shin Soung-Cheal;Song Hye-Soon;Hong Young-Seoub;Kwak Jong-Young;Yoo Byung-Chul;Lee Yong-Hwan
    • Journal of Life Science
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    • 제16권2호
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    • pp.199-205
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    • 2006
  • Peroxisome proliferator activated receptor (PPAR)-$\alpha$ of three PPAR subtypes ($-\alpha,\;-\beta/-\gamma,\;-\delta$), which are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in lipoprotein and glucose homeostasis. A variation in the PPAR-a gene expression has been suggested to influence the development of metabolic syndrome through alterations in lipid concentrations. The aim of our study was to investigate the association between the PPAR-a and metabolic syndrome among South Korean. A total of 542 health screen examinees were enrolled in this study who were examined in Kosin University Gospel Hospital from December, 2004 to July, 2005. The height, weight, waist circumference, and systolic and diastolic blood pressure of the subjects were examined and fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride were measured by-sampling in venous blood. The metabolic syndrome was defined as the presence of three or more of the following : waist circumference men ${\geq}90cm$, women ${\geq}80cm$, blood pressure ${\geq}130/85mmHg$, fasting glucose ${\geq}110mg/dL$, HDL cholesterol men <40 mg/dL, women <50 mg/dL, triglyceride ${\geq}150mg/dL$. The blood pressure, fasting glucose, HDL cholesterol, triglyceride were evaluated by using the criteria of NECP ATP III and waist circumference was assessed by using the criteria of WHO Asia-Western Pacific. And the author compared the frequency of the PPAR-$\alpha$ mutation of L162V ($C{\rightarrow}G$ variant in exon 5) in a sample of 542 subjects with and without the metabolic syndrome by polymerase chain reaction allele-specific oligonucleotide (PCR-ASO) method. One (0.2%) hetero-isotype among high risk of metabolic syndrome was identified. The values of waist circumference, body mass index and low density lipoprotein cholesterol of the mutant were 100 cm, 28.6 $kg/m^2$ and 120 mg/dL, respectively. Although the author failed to see significant association between the presence of the PPAR-$\alpha$ L162V polymorphism and metabolic syndrome, one PPAR-$\alpha$ L162V polymorphism in metabolic syndrome patients was found.

Susceptibility Weighted Image for Stem Cell Tracking in Rat Photothrombotic Infarction (흰쥐 광 혈전 뇌경색 모델에서 줄기세포 추적을 위한 자화강조영상)

  • Ha, Bon-Chul;Lim, Cheong-Hwan
    • The Journal of the Korea Contents Association
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    • 제10권8호
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    • pp.249-256
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    • 2010
  • To the detect of SPIO-labelled hMSC, in vitro study on various cell concentration and in vivo molecular magnetic resonance imaging(MRI) technique using T2, $T2^*$ and SWI are compared with pathology. Cell concentration was $1.56{\times}10^4$, $3.13{\times}10^4$, $6.25{\times}10^4$, $1.25{\times}10^5$, $2.5{\times}10^5$, $5{\times}10^5\;cells/m{\ell}$ and for control $5{\times}10^5\cells/m{\ell}$. MRI technique using T2, $T^2$ and SWI. Photothrombotic infarction was located 2.5mm from bregma right, posterior. Cell injected through the tail vein of rat for 8 rats. MRI performed pre injection and post injection of 1, 3, 7 and 14days and sacrifice for pathology. MRI analysed on quantitatively. In vitro result, SWI was highest CNR as compared with $T2^*WI$, T2WI and $2.5{\times}10^5\;cells/m{\ell}$ cell concentration. In vivo result among the T2WI, $T2^WI$, SWI, T2WI is highest CNR between normal and infarction. CNR in normal-SPIO and infarction-SPIO is high score in SWI. Therefore, T2WI is good distinguish between normal and infarction, SWI are well detect SPIO-labelled hMSC from normal and infarction. Nowaday, SWI are mostly used on hemorrhage, calcification etc. in clinically, but for the future, stem cell therapy is commonly application at all disease which is good observing tool for SPIO-labelled stem cells.

The Relationship between Intracellular Protein Kinase C Concentration and Invasiveness in U-87 Malignant Glioma Cells (교모세포종 세포주 U-87에서 세포내 PKC 농도와 종양침습성과의 상관 관계)

  • Ji, Cheol;Cho, Kyung-Keun;Lee, Kyung Jin;Park, Sung Chan;Cho, Jung Ki;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
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    • 제30권3호
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    • pp.263-271
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    • 2001
  • Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

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The Relationship between Heme Oxygenase-1 Expression and Response to Cisplatin Containing Chemotherapy in Advanced Non-Small Cell Lung Cancer (진행성 비소세포폐암에서 Heme oxygenase-1 발현과 Cisplatin을 포함하는 항암화학요법의 치료반응과의 연관성)

  • Yang, Doo Kyung;Roh, Mee Sook;Lee, Kyung Eun;Kim, Ki Nam;Lee, Ki Nam;Choi, Pil Jo;Bang, Jung Hee;Kim, Bo Kyung;Seo, Hyo Rim;Kim, Min Ji;Kim, Seul Ki;Lee, Soo-Keol;Son, Choon Hee
    • Tuberculosis and Respiratory Diseases
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    • 제60권3호
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    • pp.314-320
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    • 2006
  • Background : The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. Material and Methods : The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. Results : Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. Conclusion : HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.

The Role of Heme Oxygenase-1 in Lung Cancer Cells (폐암세포주에서 Heme Oxygenase-1의 역할)

  • Jung, Jong-Hoon;Kim, Hak-Ryul;Kim, Eun-Jung;Hwang, Ki-Eun;Kim, So-Young;Park, Jung-Hyun;Kim, Hwi-Jung;Yang, Sei-Hoon;Jeong, Eun-Taek
    • Tuberculosis and Respiratory Diseases
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    • 제60권3호
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    • pp.304-313
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    • 2006
  • Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.

The Efficacy of Endovascular Treatment for Deep Vein Thrombosis (하지 심부정맥 혈전증에서 중재적 치료의 유용성)

  • Kim, Seon-Hee;Chung, Sung-Woon;Kim, Chang-Won
    • Journal of Chest Surgery
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    • 제43권3호
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    • pp.266-272
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    • 2010
  • Background: Deep vein thrombosis (DVT) is a serious disease that causes life-threatening pulmonary embolism and chronic venous insufficiency. Anticoagulation is the standard therapy for DVT. However, the results of standard anticoagulation for treating DVT have been disappointing, so endovascular treatment is commonly performed nowadays. The aim of this study was to evaluate the efficacy of an endovascular procedure for treating patients with DVT. Material and Method: We retrospectively evaluated the clinical data of 29 DVT patients who underwent an endovascular procedure between December 2006 and July 2008. We compared the results of the 29 patients with the results of another 45 patients who were treated with only aspirin and heparin. Result: The patient’s mean age was 55.4 years in the intervention group and 53.7 years in the control group. DVT occurred more frequently in the females. Catheter-directed thrombolysis was performed in 22 patients (75.8%). Aspiration thrombectomy was performed in 18 patients (62%) and a endovascular stent was placed in 25 patients (86.2%). Fifteen patients (51.7%) underwent percutaneous insertion of a retrievable IVC filter for the prevention of pulmonary embolism. In the control group, thirty nine patients (86.7%) were treated with low-molecular heparin, and seven patients (15.6%) who were contraindicated for warfarin were treated with aspirin. No bleeding complications occurred during thrombolysis or anticoagulation. We analyzed the statistical data according to recurrence of DVT and the incidence of post-thrombotic syndrome (PTS) during the follow-up period. The intervention group had a significantly lower incidence of PTS (p-value=0.008), but they had the same result as the control group for the recurrence of DVT. In addition, death from the DVT did not occur in the intervention group. Thus, we obtained better clinical outcomes in the intervention group as compared to those in the anticoagulation only group. Conclusion: Endovascular procedures are effective alternative modalities, as compared to systemic anticoagulation, for the treatment of DVT. But more studies are needed to determine the specific indications and to validate the long-term efficacy of endovascular procedures for the treatment of DVT.

Comparison of Urine Iodine/Creatinine ratio between Patients following Stringent and Less Stringent Low Iodine Diet for Radioiodine Remnant Ablation of Thyroid Cancer (갑상선암의 방사성요오드치료를 위한 저요오드식이 방법 차이에 따른 소변 중 요오드/크레아티닌 비의 비교)

  • Roh, Jee-Ho;Kim, Byung-Il;Ha, Ji-Su;Chang, Sei-Joong;Shin, Hye-Young;Choi, Joon-Hyuk;Kim, Do-Min;Kim, Chong-Soon
    • Nuclear Medicine and Molecular Imaging
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    • 제40권6호
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    • pp.322-326
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    • 2006
  • A low iodine diet (LID) for $1{\sim}2$ weeks is recommended for patients who undergoing radioiodine remnant ablation. However, the LID educations for patients are different among centers because there is no concrete recommendation for protocol of LID. In this investigation, we compared two representative types of LID protocols performed in several centers in Korea using urine iodine to creatinine ratio (urine I/Cr). Methods: From 2006, April to June, patients referred to our center for radioiodine remnant ablation of thyroid cancer from several local hospitals which had different LID protocols were included. We divided into two groups, stringent LID for 1week and less stringent LID for 2 weeks, then measured their urine I/Cr ratio with spot urine when patients were admitted to the hospital. Results: Total 27 patients were included in this investigation (M:F=1:26; 13 in one-week stringent LID; 14 in two-week less stringent LID. Average of urine I/Cr ratio was $127.87{\pm}78.52{\mu}g/g$ in stringent LID for 1 week, and $289.75{\pm}188.24{\mu}g/g$ in less stringent LID for 2 weeks. It was significantly lower in stringent LID for 1 week group (p=0.008). The number of patients whose urine I/Cr ratios were below $100{\mu}g/g$ was 6 of 13 in stringent LID for 1 week group, and 3 of 14 in less stringent LID for 2 weeks group. Conclusion: Stringent LID for 1 week resulted in better urinary I/Cr ratio in our investigation compared with the other protocol. However it still resulted in plenty of inadequate range of I/Cr ratio, so more stringent protocol such as stringent LID for 2 weeks is expected more desirable.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

  • Xiong, Wei;Jiang, Yong-Xin;Ai, Yi-Qin;Liu, Shan;Wu, Xing-Rao;Cui, Jian-Guo;Qin, Ji-Yong;Liu, Yan;Xia, Yao-Xiong;Ju, Yun-He;He, Wen-Jie;Wang, Yong;Li, Yun-Fen;Hou, Yu;Wang, Li;Li, Wen-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3395-3402
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    • 2015
  • Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

Development of $^1H-^{31}P$ Animal RF Coil for pH Measurement Using a Clinical MR Scanner (임상용 MR에서 pH 측정을 위한 동물 실험용 $^1H-^{31}P$ RF 코일 개발)

  • Kim, Eun Ju;Kim, Daehong;Lee, Sangwoo;Heo, Dan;Lee, Young Han;Suh, Jin-Suck
    • Investigative Magnetic Resonance Imaging
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    • 제18권1호
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    • pp.52-58
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    • 2014
  • Purpose : To establish a pH measurement system for a mouse tumor study using a clinical scanner, to develop the $^1H$ and 31P radio frequency (RF) coil system and to test pH accuracy with phantoms. Materials and Methods: The $^1H$ and the $^{31}P$ surface coils were designed to acquire signals from mouse tumors. Two coils were positioned orthogonally for geometric decoupling. The pH values of various pH phantoms were calculated using the $^1H$ decoupled $^{31}P$ MR spectrum with the Henderson-Hasselbalch equation. The calculated pH value was compared to that of a pH meter. Results: The mutual coil coupling was shown in a standard $S_{12}$. Coil coupling ($S_{12}$) were -73.0 and -62.3 dB respectively. The signal-to-noise ratio (SNR) obtained from the homogeneous phantom $^1H$ image was greater than 300. The high resolution in vivo mice images were acquired using a $^{31}P$-decoupled $^1H$ coil. The pH values calculated from the $^1H$-decoupled $^{31}P$ spectrum correlated well with the values measured by pH meter ($R^2$=0.97). Conclusion: Accurate pH values can be acquired using a $^1H$-decoupled $^{31}P$ RF coil with a clinical scanner. This two-surface coil system could be applied to other nuclear MRS or MRI.

In Vitro Uptakes of Radiolabeled IVDU and IVFRU in Herpes Simplex Virus Type-1 Thymidine Kinase (HSV1-tk) Gene Transduced Morris Hepatoma Cell Line (단순 헤르페스 제 1형 티미딘 키나제 유전자 이입 간암세포주에서 방사표지 IVDU와 IVFRU의 섭취 평가)

  • Lee, Tae-Sup;Choi, Tae-Hyun;Ahn, Soon-Hyuk;Woo, Kwang-Sun;Jeong, Wee-Sup;Kwon, Hee-Chung;Awh, Ok-Doo;Choi, Chang-Woon;Lim, Sang-Moo
    • The Korean Journal of Nuclear Medicine
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    • 제38권1호
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    • pp.62-73
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    • 2004
  • Purpose: The herpes simplex virus type 1 thymidine kinase gene(HSV1-tk) is an attractive candidate as a reporter gene in noninvasive reporter gene monitoring system. The HSV1-tk gene was chosen as a reporter gene, because it has been extensively studied, and there are appropriate reporter probes, substrates of HSV1-tk gene product, to apply for HSV1-tk gene imaging. We used radiolabeled 5-iodovinyl-2'-deoxyuridine (IVDU) and 5-iodovinyl-2'-fluoro-2'-deoxyuridine (IVFRU) as reporter probes for HSV1-tk gene monitoring system. Materials and Methods: We prepared HSV1-tk gene transduced Morris hepatoma cell line using retroviral vector, MOLTEN containing HSV1-tk gene. And we confirmed the HSV1-tk gene expression by Northern blotting and Western blotting. We compared in vitro uptakes of radioiodinated IVDU and IVFRU to monitor HSV1-tk gene expression in Morris hepatoma cell line (MCA) and HSV1-tk gene tranduced MCA (MCA-tk) cells until 480 minutes. We also peformed correlation analysis between percentage of HSV1-tk gene tranduced MCA cell % (MCA-tk%) and uptakes of radiolabeled IVDU or IVFRU. Results: MCA-tk cell expressed HSV1-tk mRNA and HSV1-TK protein. Two compounds showed minimal uptake in MCA, but increased uptake was observed in MCA-tk. IVDU showed 4-fold higher accumulation than IVFRU at 480 min in MCA-tk (p<0.01). Both IVDU and IVFRU uptake were linearly correlated ($R^2>0.96$) with increasing MCA-tk%. Conclusion: The radiolabeld IVDU and IVFRU showed higher specific accumulation in retrovirally HSV1-tk gene transfected Morris hepatoma cell line. Both IVDU and IVFRU could be used as good substrates for evaluation of HSV1-tk gene expression.