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Extract from Eucheuma cottonii Induces Apoptotic Cell Death on Human Osteosarcoma Saos-2 Cells via Caspase Cascade Apoptosis Pathway (Eucheuma cottonii 추출물에 의한 인체 골육종암 Saos-2 세포의 자가사멸 유도)

  • Kang, Chang-Won;Kang, Min-Jae;Kim, Kyong Rok;Kim, Nan-Hee;Seo, Yong Bae;Kang, Keon-Hee;Kim, Sang-Ho;Kim, Gun-Do
    • Journal of Life Science
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    • v.26 no.2
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    • pp.147-154
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    • 2016
  • Osteosarcoma (OS) is the most common and malignant bone tumors. Although many types of resection surgery and experimental agents were developed, median survival and clinical prognosis are poorly investigated. Recently, several researches have reported that Eucheuma cottonii has potent as protective effects of coal dust-induced lung damage via inhibition of malondialdehyde (MDA) and oxidative stress in bronchoalveolar lavage fluids (BALF). However, anti-cancer effects and specific molecular mechanism of extract from Eucheuma cottonii (EE) has not been clearly studied yet. This study evaluated that anti-cancer potential of EE in human osteosarcoma Saos-2 cells. EE indicated cytotoxicity on Saos-2 cells in a dose-dependent manner. Morphological degradation and nucleic condensation were also observed under the EE treatment. However, it did not significantly affect on non-cancerous kidney HEK-293 cells under the same concentration which is shown cytotoxicity on Saos-2 cells. The phosphorylation of Fas-Associated Death Domain (FADD) and expression of cleaved caspase-8, -7 and -3 were upregulated in a dose-dependent manner. In immunofluorescence staining, expression level of Fas and cleaved PARP were upregulated by EE treatment. Furthermore, treatment of EE induces upregulation of sub G1 phase by flow cytometry analysis. The results demonstrated that EE has a therapeutic potential against osteosarcoma via FADD mediated caspase cascade apoptosis signal pathway.

Molecular Miology of the Poliovirus (폴리오바이러스의 분자생물학)

  • 최원상
    • Journal of Life Science
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    • v.7 no.4
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    • pp.392-401
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    • 1997
  • The poliovirus is a small, and non-enveloped virus. The RNA genome of poliovirus is continuous, linear, and has a single open reading frame. This polyprotein precursor is cleaved proteolytically to yield mature products. Most of the cleavages occur by viral protease. The mature proteins derived from the P1 polyprotein precursor are the structural components of the viral capsid. The initial cleavage by 2A protease is indirectly involved in the cleavage of a cellular protein p220, a subunit of the eukaryotic translation initiation factor 4F. This cleavage leads to the shut-off of cap-dependent host cell translation, and allows poliovirus to utilize the host cell machinery exclusively for translation its own RNA, which is initiated by internal ribosome entry via a cap-independent mechanism. The functional role of the 2B, 2C and 2BC proteins are not much known. 2B, 2C, 2BC and 3CD proteins are involved in the replication complex of virus induced vesicles. All newly synthesized viral RNAs are linked with VPg. VPg is a 22 amino acid polypeptide which is derived from 3AB. The 3C and 3CD are protease and process most of the cleavage sites of the polyprotein precursor. The 3C protein is also involved in inhibition of RNA polymerase II and III mediated transcription by converting host transcription factor to an inactive form. The 3D is the RNA dependent RNA polymerase. It is known that poliovirus replication follows the general pattern of positive strand RNA virus. Plus strand RNA is transcribed into complementary minus strand RNA that, in turn, is transcribed for the synthesis of plus strand RNA is transcribed into complementary minus strand RNA that, in turn, is transcribed for the synthesis of plus strand RNA strands. Poliovirus RNA synthesis occurs in a membranous environment but how the template RNA and proteins required for RNA replication assemble in the membrane is not much known. The RNA requirements for the encapsidation of the poliovirus genome (packaging signal) are totally unknown. The poliovirus infection cycle lasts approximately 6 hours.

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A Clinical Study of Hypersensitive rhinitis including Allergic rhinitis (알레르기성 비염을 포함하는 과민성 비염 환자에 관한 임상적 연구)

  • Choi, In-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.15 no.2
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    • pp.169-182
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    • 2002
  • Background: Allergic rhinitis(AR) is a heterogeneous disorder that despite its high prevalence is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. And it is frequently accompanied by symptoms involving the eyes, ears, and throat, including postnasal drainage. There are many different causes of rhinitis in children and adults. Approximately 50$\%$ of all cases of rhinitis are caused by allergy. In the case of rhinitis caused by allergens, symptoms arise as a result of inflammation induced by a gamma globulin E-mediated immune response to specific allergens such as pollens, molds, animal dander, and dust mites. The immune response involves the release of inflammatory mediators and the activation and recruitment of cells to the nasal mucosa. AR is similar to 鼻?, hypersensitive rhinitis in Oriental Medicine. I think hypersensitive rhinitis is including of AR, vasomotor rhinitis and non-allergic rhinitis related with eosinophil increased and so on. Purpose: To perform a clinical analysis of hypersensitive rhinitis including allergic rhinitis and estimate the efficacy of Oriental Medical treatment. Objective: We studied 96 patients who had visited our hospital with complaints of nasal symptoms from March 2000 to February 2002; they had the signs more than 2 - nasal obstruction, watery discharge, sneezing and eye or nasal itching. Parameters Observed & Methods: We treated them with acupuncture & herb-medication. Sometime they used aroma oil or external medicine. 1) the distribution of sex & age groups 2) the clinical type based on duration & the severity of symptom 3) the breakdown of complication & pasl history of Otolaryngologic or allergic disease 4) the clinical assessment and classification of rhinitis(sneezers and runners & blockers) 5) the associated symptoms and signs 6) the classification of Byeonjeung 7) the classification of prescriptions and 8) the efficacy of treatment. Result: 1. In the clinical type of based on duration, the intermittent type was 42.7$\%$ and the persistent was 57.3$\%$. 2. We observed the severity of symptoms based on the quality of life. The mild type was 24.0$\%$ and the moderate-severe was 76.0$\%$. 3. In the clinical assessment and classification of rhinitis, the sneezers and runners type was 69.8$\%$ and the blockers was 30.2$\%$. 4. The most common family history with otolaryngologic or allergic disease were allergic rhinitis(17.7$\%$), urticaria, paranasal sinusitis and T.B.(3.1$\%$). 5. The most common past history with otolaryngologic or allergic disease were paranasal sinusitis(14.6$\%$), atopic dermatitis and asthma(8.3$\%$). It was 31.3$\%$ they had a family history and 44.8$\%$, past history. 6. The most common complication was paranasal sinusitis(15.6$\%$). In decreasing order the others were otitis media with effusion(9.4$\%$), GERD and headache(6.3$\%$), asthma, bronchitis, nasal bleeding and allergic dermatitis(5.2$\%$). 7. Classification through Byeonjeung : ⅰ) 39 cases(34.9$\%$) were classified as showing Deficiency syndrome. The insuffficiency of Qi was 17.7$\%$, deficiency of Kidney-Yang, 12.5$\%$ and Lung-Cold, 10.4$\%$. ⅱ) 57 cases(59.4$\%$) were classified as showing Excess syndrome. The Fever of YangMing-meridian was 35.4$\%$, Lung-Fever, 24.0$\%$. 8. The efficacy of treatments showed: an improvement in 22cases(22.9$\%$); an improvement partly in 24 cases(25.0$\%$); no real improvement or changes in 16 cases(16.7$\%$); and couldn't check the results 18cases(18.6$\%$). Conclusion: We suggest that this study could be utilized as a standard of clinical Oriental Medical treatment when we treat hypersensitive rhinitis including allergic rhinitis.

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Artificial Intelligence In Wheelchair: From Technology for Autonomy to Technology for Interdependence and Care (휠체어 탄 인공지능: 자율적 기술에서 상호의존과 돌봄의 기술로)

  • HA, Dae-Cheong
    • Journal of Science and Technology Studies
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    • v.19 no.2
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    • pp.169-206
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    • 2019
  • This article seeks to explore new relationships and ethics of human and technology by analyzing a cultural imaginary produced by artificial intelligence. Drawing on theoretical reflections of the Feminist Scientific and Technological Studies which understand science and technology as the matter of care(Puig de la Bellacas, 2011), this paper focuses on the fact that artificial intelligence and robots materialize cultural imaginary such as autonomy. This autonomy, defined as the capacity to adapt to a new environment through self-learning, is accepted as a way to conceptualize an authentic human or an ideal subject. However, this article argues that artificial intelligence is mediated by and dependent on invisible human labor and complex material devices, suggesting that such autonomy is close to fiction. The recent growth of the so-called 'assistant technology' shows that it is differentially visualizing the care work of both machines and humans. Technology and its cultural imaginary hide the care work of human workers and actively visualize the one of the machine. And they make autonomy and agency ideal humanness, leaving disabled bodies and dependency as unworthy. Artificial intelligence and its cultural imaginary negate the value of disabled bodies while idealizing abled-bodies, and result in eliminating the real relationship between man and technology as mutually dependent beings. In conclusion, the author argues that the technology we need is not the one to exclude the non-typical bodies and care work of others, but the one to include them as they are. This technology responsibly empathizes marginalized beings and encourages solidarity between fragile beings. Inspired by an art performance of artist Sue Austin, the author finally comes up with and suggests 'artificial intelligence in wheelchair' as an alternative figuration for the currently dominant 'autonomous artificial intelligence'.

Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

  • Ji Yoon Kim;Un Chul Shin;Ji Yong Park;Ran Ji Yoo;Soeku Bae;Tae Hyeon Choi;Kyuwan Kim;Young Chan Ann;Jin Sil Kim;Yu Jin Shin;Hokyu Lee;Yong Jin Lee;Kyo Chul Lee;Suhng Wook Kim;Yun-Sang Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.9-16
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    • 2023
  • Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

Comparison of the Uptakes of Tc-99m MIBI and Tc-99m Tetrofosmin in A549, an MRP-expressing Cancer Cell, In Vitro and In Vivo (MRP발현 인체 비소세포 폐암 A549에서 Tc-99m MIBI와 Tc-99m Tetrofosmin섭취의 비교)

  • Yoo, Jeong-Ah;Jeong, Shin-Young;Seo, Myung-Rang;Bae, Jin-Ho;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Choi, Sang-Woon;Lee, Byung-Ho;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.6
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    • pp.382-392
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    • 2003
  • Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein (P-Glycoprotein과 Multidrug Resistance Associated Protein을 발현하는 암세포와 종양에서 Tc-99m Sestamibi와 Tc-99m Tetrofosmin의 섭취율 비교)

  • Cho, Jung-Ah;Lee, Jae-Tae;Yoo, Jung-Ah;Seo, Ji-Hyoung;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Sohn, Sang-Gyun;Ha, Jeoung-Hee;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.1
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    • pp.34-43
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    • 2005
  • Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.