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Evaluation of Combined Contrast Agent using N-(p-maleimidophenyl) Isocyanate Linker-mediated Synthesis for Simultaneous PET-MRI (동시 PET-MRI를 위한 N-(p-maleimidophenyl) isocyanate linker-매개 합성을 이용한 복합 조영제의 평가)

  • Lee, Gil-Jae;Lee, Hwun-Jae;Lee, Tae-Soo
    • Journal of the Korean Society of Radiology
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    • v.16 no.2
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    • pp.103-113
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    • 2022
  • In this paper, a combined 18F-FDG(fluorodeoxyglucose) and MNP(magnetic nanoparticles) contrast agent was synthesized using N-(p-maleimidophenyl) isocyanate as the crosslinker for use in simultaneous PET-MRI scans. PET-MRI images were acquired and evaluated before and after injection of the combined contrast imaging agent (18F-FDG labeled MNP) from a glioma stem cell mouse model. After setting the region of interest (ROI) on each acquired image, the area of the lesion was calculated by segmentation. As a result, the PET image was larger than the MRI. In particular, the simultaneous PET-MRI images showed accurate lesions along with the surrounding soft tissue. The mean and standard deviation values were higher in the MRI images alone than in the PET images or the simultaneous PET-MRI images, regardless of whether the contrast agent was injected. In addition, the simultaneous PET-MRI image values were higher than for the PET images. For PSNR experiments, the original image was PET Image using 18F-FDG, MRI using MNPs, and MRI without contrast medium, and the target image was simultaneous PET-MRI image using 18F-FDG labeled MNPs contrast medium. As a result, all of them appeared significantly, suggesting that the 18F-FDG labeled MNPs contrast medium is useful. Future research is needed to develop an agent that can simultaneously diagnose and treat through SPECT-MRI imaging research that can use various nuclides.

Technical Review of Target Volume Delineation on the Posterior Fossa Tumor : An Optimal Head and Neck Position (후두와 종양의 방사선치료 시 표적용적의 결정을 위한 적절한 치료자세 연구)

  • Yoon Sang Min;Lee Sang-wook;Ahn Seung Do;Kim Jong Hoon;YE Byong Yong;Ra Young Shin;Kim Tae Hyung;Choi Eun Kyung
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.94-99
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    • 2003
  • Purpose : To explore a 3D conformal radiotherapy technique for a posterior fossa boost, and the potential advantages of a prone position for such radiotherapy. Materials and Methods :A CT simulator and 3D conformal radiotherapy Planning system was used for the posterior fossa boost treatment on a 13-year-old medulloblastoma patient. He was placed In the prone position and Immobilized with an aquaplast mask and immobilization mold. CT scans were obtained of the brain from the top of the skull to the lower neck, with IV contrast enhancement. The target volume and normal structures were delineated on each slice, with treatment planning peformed using non-coplanar conformal beams. Results : The CT scans, and treatment In the prone position, were peformed successfully. In the prone position, the definition of the target volume was made easier due to the well enhanced tentorium, In audition, the posterior fossa was located anteriorly, and with the greater choice of beam arrangements, more accurate treatment planning was possible as the primary beams were not obstructed by the treatment table. Conclusion : .A posterior fossa boost, in the prone position, Is feasible in cooperating patients, but further evaluation is needed to define the optimal and most comfortable treatment positions.

Location Error of the Dens in a Two-Dimensional Set-up Verification During Head and Neck Radiotherapy (뇌.두경부 방사선치료 시 전자조사문영상장치를 이용한 세트업 오차 확인에서 제2경추 치상돌기 위치의 임상적 의의)

  • Kim, Dong-Hyun;Kim, Won-Taek;Ki, Yong-Gan;Nam, Ji-Ho;Lee, Mi-Ran;Jeon, Ho-Sang;Park, Dal;Kim, Dong-Won
    • Radiation Oncology Journal
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    • v.29 no.2
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    • pp.107-114
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    • 2011
  • Purpose: To assess the degree and clinical impact of location error of the dens on the X-axis during radiotherapy to brain and head and neck tumors. Materials and Methods: Twenty-one patients with brain tumors or head and neck tumors who received three-dimensional conformal radiation therapy or intensity-modulated radiation therapy from January 2009 to June 2010 were included in this study. In comparison two-dimensional verification portal images with initial simulation images, location error of the nasal septum and the dens on the X-axis was measured. The effect of set-up errors of the dens was simulated in the planning system and analyzed with physical dose parameters. Results: A total of 402 portal images were reviewed. The mean location error at the nasal septum was 0.16 mm and at the dens was 0.33 mm (absolute value). Location errors of more than 3 mm were recorded in 43 cases (10.7%) at the nasal septum, compared to 133 cases (33.1%) at the dens. There was no case with a location error more than 5 mm at the nasal septum, compared to 11 cases (2.7%) at the dens. In a dosimetric simulation, a location error more than 5 mm at the dens could induce a reduction in the clinical target volume 1 coverage (V95: 100%${\rightarrow}$87.2%) and overdosing to a critical normal organ (Spinal cord V45: <0.1%${\rightarrow}$12.6%). Conclusion: In both brain and head and neck radiotherapy, a relatively larger set-up error was detected at the dens than the nasal septum when using an electronic portal imaging device. Consideration of the location error of the dens is necessary at the time of the precise radiation beam delivery in two-dimensional verification systems.

Effect of Simultaneous Use of Platelet Glycoprotein IIb / IIIa Receptor Blocker and Thrombus Aspiration in Patients with Coronary Artery Stent Thrombosis (관상동맥 스텐트 혈전증 환자에서 혈소판 당단백 IIb/IIIa 수용체 차단제와 혈전흡입술 동시시행의 임상결과)

  • Kim, In Soo;Choi, Nam Gil;Kong, Chang gi;Eun, Sung jong;Han, Jae Bok
    • Journal of the Korean Society of Radiology
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    • v.13 no.3
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    • pp.359-369
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    • 2019
  • To evaluate the effect of simultaneous use of platelet glycoprotein IIb / IIIa receptor blocker and catheter assisted thrombus aspiration in the treatment of coronary stent thrombosis. 267 patients ($64.6{\pm}12.1years$, 187 men) with stent thrombosis on coronary angiography at Chonnam National University Hospital from July 2008 to July 2017 were enrolled. We devided two groups based on treatment modalities: Group I (N=32, platelet glycoprotein IIb / IIIa receptor blocker and thrombo-aspiration), Group II (N =235, either platelet glycoprotein IIb /IIIa receptor blocker or thrombo-aspiration, or none of both), and the major cardiac events including death, revascularization and stent thrombosis were followed up for 1 year. There were no significant differences in clinical characteristics between the two groups including age (Group I: $60.8{\pm}12.9$ vs. Group II: $65.1{\pm}11.9$, p= 0.603), male (Group I: 75.0% vs. Group II: 69.4%, p=0.681), and left ventricular ejection fraction (Group I: $58.1{\pm}9.0%$ vs. Group II: $59.5{\pm}11.9%$, p= 0.127). The major cardiac events did not differ between the two groups (Group I: 12.5% vs. Group II: 23.8%, p=0.180). The secondary endopoints were as followings: The mortality rate (Group I: 0% vs. 13.2%, Group II: p=0.034), target lesion revascularization (Group I: 9.4% vs Group II: 6.4%, p=0.461) and stent thrombosis (Group I: 3.1% vs. Group II: 4.7%, p=1.000). In conclusion, in the treatment of coronary artery stent thrombosis, simultaneous use of platelet glycoprotein IIb / IIIa receptor blocker and thrombus aspiration was associated with better clinical outcomes regarding 1 year mortality.

Experimental Studies on the Antitumor Effects of Jinryungtang Gagambang Extract (진령탕가감방의 항종양효과(抗腫瘍效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Jeong, Jun-Tak;Moon, Goo;Moon, Suk-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.37-53
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    • 1998
  • The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.

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Bidirectional Cross-talk Between Estrogen Receptor and Growth Factor Receptors in Breast Cancer Cell (유방암세포에서 에스트로겐 수용체와 성장인자 수용체 사이의 양방향 상호작용)

  • Min, Gyesik
    • Journal of Life Science
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    • v.28 no.2
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    • pp.265-273
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    • 2018
  • Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

Synergistic antitumor activity of ST1571 and camptothecin in human cancer cells (Camptothecin 에 의한 ST1571 의 항암 활성 증강)

  • Kim, Mi-Ju;Lee, Sang-Min;Bae, Jae-Ho;Chung, Byung-Seon;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.748-755
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    • 2007
  • The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

Inhibitory Effects of CD99-derived Peptide CD99CRIII3 on the Extravasation of Monocytes and Inflammatory Reactions in Contact Dermatitis Mouse Model (접촉성 피부염 마우스 모델에서 단핵구의 유출 및 염증 반응에 대한 CD99-유래 펩타이드 CD99CRIII3의 억제 효과)

  • Ju, Hyun-Mi;Park, Kyeong-Han
    • Anatomy & Biological Anthropology
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    • v.31 no.4
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    • pp.143-149
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    • 2018
  • Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates ${\beta}1$ integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased ${\beta}1$-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.

Effects of Inhibitors on the Function and Activity of Topoisomerase, and Gene Expression in HL-60 Human Leukemia Cells (HL-60 세포의 유전자 발현 및 topoisomerase의 기능 활성에 미치는 억제제의 영향)

  • Jeong, In-Cheol;Cho, Moo-Youn;Park, Jang-Su
    • Journal of Life Science
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    • v.18 no.1
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    • pp.75-83
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    • 2008
  • This studies were designed to elucidate whether inhibitors of topoisomerase regulate function and activity of topoisomerase, and gene expression in HL-60 human leukemia cells. HL-60 cells were treated with 10-hydroxycamptothecin or doxorubicin, total RNA was isolated, and expressed genes were investigated with human oligonucleotide microarray containing 10K gene, respectively. Expression profiles of the human leukemia HL-60 cells treated with 10-hydroxycamptothecin (10-CIT) or doxorubicin associated with signal transduction,. cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription and immune response, especially genes related with transcription and cell growth. In HL-60 cells treated with 10-CPT, the expression of topoisomerase III${\alpha}$, III${\beta}$ and I gene from oligo chip microarray analysis were increased over, but the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were decreased over. In contrast, the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were increased over in HL-60 cells treated with doxorubicin, whereas the expression of topoisomerase III${\alpha}$ and III${\beta}$ mRNA remained no significant change. These results suggest that these data may be useful for novel therapeutic markers.

Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.