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Inhibition of Gastric Cancer Cell Cycle Progression by ${\gamma}$ -Tubulin Antisense Oligonucleotides

  • Hwang, Sun-Hee;Kim, Myung-Won;Park, Sang-Kyu;Noh, Jung-Woo;Han, In-Seob
    • Journal of Microbiology and Biotechnology
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    • v.11 no.5
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    • pp.876-879
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    • 2001
  • ${\gamma}$ -Tubulin is an essential component involved in microtubule nucleation. The present work examined whether the fast proliferation of cancer cells can be retarded by the depletion of ${\gamma}$ -tubulin expression. Two different gastric cancer cell lines and one control cell line were treated with antisence oligonucleotides complementary to the messenger RNA of ${\gamma}$ -tubulin. The$[^3H]$ -thymidine incorporation in the two gastric cancer cell lines, SNU-1 and SNU-216, was dramatically reducd by treatment with the ${\gamma}$ -tubulin antisense oligonucleotides in a dosage-dependent manner. In contrast, the control cell line, NIH/3T3, showed no significant effect from the antisense oligonucleotides even at a high concentration. The ablation of ${\gamma}$ -tubulin expression in the tumor cells resulted in an altered DNA synthesis during mitosis and it decreased the cell progression. Accordingly, the use of antisense oligonucleotides may be an effective way of inhibiting the proliferation of human gastric cancers.

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PD-L1 Targeted Immunoliposomes with PD-L1 siRNA and HDAC Inhibitor for Anti-Lung Cancer Immunotherapy

  • Se-Yun Hong;Seong-Min Lee;Pyung-Hwan Kim;Keun-Sik Kim
    • Biomedical Science Letters
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    • v.28 no.4
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    • pp.247-259
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    • 2022
  • Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

Dendritic Cell Based Cancer Immunotherapy: in vivo Study with Mouse Renal Cell Carcinoma Model (수지상세포를 이용한 항암 면역 치료: 생쥐 신장암 모델을 이용한 연구)

  • Lee, Hyunah;Choi, Kwang-Min;Baek, Soyoung;Lee, Hong-Ghi;Jung, Chul-Won
    • IMMUNE NETWORK
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    • v.4 no.1
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    • pp.44-52
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    • 2004
  • Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

Design of flow path with 2 inlet and outlets to improve cell performance and prevent cell degradation in Solid Oxide Fuel Cell (SOFC 셀 성능 향상 및 수명 저하 방지를 위한 입구와 출구 2개의 유로 설계)

  • Kim, Dongwoo;Yeom, Eunseop
    • Journal of the Korean Society of Visualization
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    • v.19 no.2
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    • pp.56-62
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    • 2021
  • Solid oxide fuel cells (SOFCs) is the high efficiency fuel cell operating at high temperatures ranging from 700-1000℃. Design of the flow paths of the fuel and air in SOFCs is important to improve cell performance and prevent cell degradation. However, the uneven distribution of current density in the traditional type having one inlet and outlet causes cell degradation. In this regard, the parallel flow path with two inlet and outlets was designed and compared to the traditional type based on computational fluid dynamics (CFD) simulation. To check the cell performance, hydrogen distribution, velocity distribution and current density distribution were monitored. The results validated that the parallel designs with two inlets and outlets have a higher cell performance compared to the traditional design with one inlet and outlet due to a larger reaction area. In case of uniform-type paths, more uniform current density distribution was observed with less cross-sectional variation in flow paths. In case of contracted and expanded inflow paths, significant improvement of performance and uniform current density was not observed compared to uniform parallel path. Considering SOFC cell with uniform current density can prevent cell degradation, more suitable design of SOFC cell with less cross-sectional variation in the flow path should be developed. This work can be helpful to understand the role of flow distribution in the SOFC performance.

Two Cases of Gastric Metastasis from Small Cell Lung Cancer (소세포 폐암에서의 위 전이 2예)

  • Yoo, Kwang-Ha;Kim, Hyung-Joong;Ahn, Chul-Min;Lee, Se-Joon;Kim, Seung-Kyu;Lee, Won-Yong
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.273-280
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    • 1999
  • This is a report of gastric metastases secondary from a primary small cell carcinoma of the lung in two men. Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the reports in the literature the prevalence of metastasis to the stomach occurs in 0.4% and the most common cell type of the primary lung carcinoma is large cell type(3.7%) followed by adenocarcinoma(2.4%), small cell carcinoma(1.7%) and squamous cell carcinoma(0.7%). The most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Most of the gastrointestinal tract metastases had no specific symptoms because of its submucosal involvement. The prognosis was poor and the mean survival period from the onset of symptoms was 49 days. The first patient was a 56-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopic findings showed two elevated mass lesions in the anterior wall of the mid body with central ulcer and the posterior wall of the fundus with intact surface mucosa. Pathologic examination of stomach tissue revealed small cell type tumor cells infiltrate in the stomach wall segmentally without destruction of the glands. The second patient was a 67-year-old man who had no other evidence of the distant metastasis. Gastroscopic findings showed a huge, oval shaped, ulcerofungating mass with deep penetrating central ulcer coated with dirty exudate in the anterior wall from mid to upper body of the stomach, and thickened elevated rugal folds in the posterior wall of the fundus. Pathologic examination of stomach tissues revealed the small cell type tumor cells showing small smudged nucleus infiltrate into the mucosa of the stomach and the architecture of mucosa intact. We report the two cases of metastatic gastric cancer from the primary small cell lung carcinoma with the literature review.

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Optical-Electronic Method for Statistical Evaluation of Human Corneal Endothelial Patterns (Human Corneal Endothelial 패턴의 통계적 분석을 위한 광전자적 방법)

  • Lee, Yim-Kul
    • Proceedings of the KOSOMBE Conference
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    • v.1992 no.11
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    • pp.58-62
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    • 1992
  • Hybrid optical-electronic procedures are introduced for the automated estimation of cell parameters (e.g., size, size variation, and shape). Two different optical Fourier analysis procedures are applied to high contrast cell boundary patterns obtained from specular micrographs of the endothelial layer. In one case, a large number of cell patterns are illuminated to extract average cell size information. Once the average cell size information has been obtained, individual cells are illuminated to extract shape information.

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Genetic Screening for Plant Cell Death Suppressors and Their Functional Analysis in Plants

  • Yun, Dae-Jin
    • Proceedings of the Korean Society of Life Science Conference
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    • 2005.04a
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    • pp.23-36
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    • 2005
  • Bax, a mammalian pro-apoptotic member of the Bcl-2 family, induces cell death when expressed In yeast. To investigate whether .Bax expression can induce cell death in plant, we produced transgenic Arabidopsis plants that contained murine Bax cDNA under control of a glucocorticoid-inducible promoter. Transgenic plants treated with dexamethasone, a strong synthetic glucocorticoid, induced Bax accumulation and cell death, suggesting that some elements of cell death mechanism by Bax may be conserved among various orgarusms. Therefore, we developed novel yeast genetic system, and cloned several Plant Bax Inhibitors (PBIs). Here, we report the function of two PBIs In detail. PBIl is ascorbate peroxidase (sAPX). Fluorescence method of dihydrorhodamine123 oxidation revealed that expression of Bax in yeast cells generated reactive oxygen species (ROS), and which was greatly reduced by co-expression with sAPX. These results suggest that sAPX inhibits the generation of ROS by Bax, which in turn suppresses Bax-induced cell death in yeast. PBI2 encodes nucleoside diphosphate kinase (NDPK). ROS stress strongly induces the expression of the NDPK2 gene in Arabidopsis thaliana (AtNDPK2). Transgenic plants overexpressing AtNDPK2 have lower lovels of ROS than wildtype plants. Mutants lacking AtNDPK2 had higher levels of ROS than wildtype. H$_{2O2}$ treatment induced the phosphorylation of two endogenous proteins whose molecular weights suggested they are AtMPK3 and AtMPK6. In the absence of H2O2 treatment, phosphorylation of these proteins was slightly elevated in plants overexpressing AtNDPK2 but markedly decreased In the AtNDPK2 deletion mutant. Yeast two-hybrid and in vitro protein pull-down assays revealed that AtNDPK2 specifically interacts with AtMPK3 and AtMPK6. Furthermore, AtNDPK2 also enhances the MBP phosphorylation activity of AtMPK3 i'n vitro. Finally, constitutive overexpression of AtNDPK2 in Arabidopsis plants conferred an enhanced tolerance to multiple environmental stresses that elicit ROS accumulation In situ. Thus, AtNDPK2 appears to play a novel regulatory role in H2O2-mediated MAPK signaling in plants.

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Basaloid Squamous Cell Carcinoma of the Lung: Two Case Reports with CT Imaging Findings (폐의 기저세포양 편평세포암: 두 개의 증례 보고와 전산화단층촬영 영상소견)

  • Joo Hee Kim;Hyun Jung Yoon;Eunju Lee;Eun Ju Kim
    • Journal of the Korean Society of Radiology
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    • v.81 no.3
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    • pp.746-752
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    • 2020
  • Basaloid squamous cell carcinoma of the lung is now considered a subtype of squamous cell carcinoma as per the 2015 WHO classification and remains a relatively unknown type of lung cancer due to its rarity. Here we report two cases of basaloid squamous cell carcinoma of the lung and their CT findings to clarify some of the radiologic features of this type of cancer. Two patients aged 85 and 68 years with lung basaloid squamous cell carcinoma visited our institution and underwent surgical resection. On CT, the lesions were 3.1 and 2.8 cm in size, respectively, well-defined, round in shape with lobulated margins and prominent intratumoral necrosis. The latter case was followed after operation for 20 months, and there was no recurrence of the disease on CT. Although very rare, basaloid squamous cell carcinoma should be considered a subtype of lung cancer in tumors sharing these CT findings.

Process Development of therapeutic antibody (ISU301) using disposable bioreactor

  • Park, Heung-Rok
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.39-39
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    • 2005
  • Large scale mammalian cell culture has become, over the past two decades, the preferred method to produce therapeutic monoclonal antibodies. In this presentation, I will introduce disposable bioreactor system and analyze key factors and points for consideration during mammalian cell culture process development. Example will be provided highlighting the selection of master cell, culture media and environmental factors based on productivity and product quality.

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A Disposable BioChip for Single Cell Manipulation

  • Yoon, Euisik
    • Proceedings of the Korean Society Of Semiconductor Equipment Technology
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    • 2004.10a
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    • pp.1-15
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    • 2004
  • o Various microfluidic components including mixromixers and micropumps have been developed for disposable biochip applications. o Single cell capturing, positioning and nanoliter drug injection chip has been demostrated. o Multi-channel, two-dimensional micro-well array has been fabricated and cell capturing and specific reagent injection have been performed.

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