• Title/Summary/Keyword: Targeted agent

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Synthesis and Characterization of a Receptor-Targeting Contrast Agent

  • Yang, Taegyun;Park, Ji-Hyung;Lee, Seung-Cheol;Kim, Cheol-Su;Cho, Jee-Hyun;Lee, Chul-Hyun;Cheong, Chae-Joon
    • Journal of the Korean Magnetic Resonance Society
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    • v.7 no.1
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    • pp.46-54
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    • 2003
  • We synthesized a contrast agent for MRI that is capable of binding to the ABP-1 receptor and enhancing the contrast of the targeted cells. We used a lysine dendrimer (G=3)DTPA[Gd] as the contrast agent and synthesized a biotinylated polyclonal antibody for ABP-1 as the first antibody. Lysine dendrimers were prepared using the solid phase peptide synthesis method.$^3$ Amino-terminated lysine dendrimers were then coupled to DTPA using the anhydride method. Gd was complexed with the DTPA-lysine dendrimer in an acidic solution of 3 eq GdCl$_3$ to one of DTPA. The lysine dendrimer-DTPA[Gd] and avidin were conjugated in MES solution, pH 6.0, using EDC as the coupling reagent. The biotin-avidin system was used to link the polyclonal antibody and contrast agent. K562 cells were used for imaging.

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Gemtuzumab ozogamicin and Antibody Engineering (Gemtuzumab ozogamicin과 항체공학)

  • Kim, Eun-Young
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.2
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    • pp.89-95
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    • 2009
  • Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.

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Enhancing Career Development Utilizing LLM for Targeted Learning Pathway (경력 개발 증진을 위한 LLM 기반 맞춤형 학습 경로 개발)

  • Mahisha Patel;Vishakha Tyagi;Isabel Hyo Jung Song
    • The Transactions of the Korea Information Processing Society
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    • v.13 no.9
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    • pp.460-467
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    • 2024
  • Targeted career development is critical for student success but is often lacking for underrepresented students at many public higher-education institutions due to insufficient career counseling resources. We propose an innovative career development tool leveraging Large Language Models (LLMs) to enhance student career prospects through three steps: (1) identifying relevant jobs by analyzing resumes, (2) pinpointing skill gaps using external resources such as classroom assignments, in addition to resumes, and (3) suggesting customized learning paths. Our tool accurately matches jobs in real-world settings, identifies true skill gaps while reducing false positives, and provides learning paths that receive high satisfaction scores from faculty. Future research will enhance the solution's capabilities by incorporating diverse external resources and leveraging advancements in LLM technology to better support early-stage career seekers.

Synthesis of Ultrasound Contrast Agent: Characteristics and Size Distribution Analysis (초음파 조영제의 합성 및 합성된 초음파 조영제의 특성 분석)

  • Lee, Hak Jong;Yoon, Tae Jong;Yoon, Young Il
    • Ultrasonography
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    • v.32 no.1
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    • pp.59-65
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    • 2013
  • Purpose: The purpose of this study is to establish the methodology regarding synthesis of ultrasound contrast agent imaging, and to evaluate the characteristics of the synthesized ultrasound contrast agents, including size or degradation interval and image quality. Materials and Methods: The ultrasound contrast agent, composed of liposome and SF6, was synthesized from the mixture solution of $21{\mu}mol$ DPPC (1, 2-Dihexadecanoyl-sn-glycero-3-phosphocholine, $C_{40}H_{80}NO_8P$), $9{\mu}mol$ cholesterol, $1.9{\mu}mol$ of DCP (Dihexadecylphosphate, $[CH_3(CH_2)_{15}O]_2P(O)OH$), and chloroform. After evaporation in a warm water bath and drying during a period of 12-24 hours, the contrast agent was synthesized by the sonication process by addition of buffer and SF6 gas. The size of the contrast agent was controlled by use of either extruder or sonication methods. After synthesis of contrast agents, analysis of the size distribution of the bubbles was performed using dynamic light scattering measurement methods. The degradation curve was also evaluated by changes in the number of contrast agents via light microscopy immediate, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, and 84 hours after synthesis. For evaluation of the role as an US contrast agent, the echogenicity of the synthesized microbubble was compared with commercially available microbubbles (SonoVue, Bracco, Milan, Italy) using a clinical ultrasound machine and phantom. Results: The contrast agents were synthesized successfully using an evaporation-drying-sonication method. The majority of bubbles showed a mean size of 154.2 nanometers, and they showed marked degradation 24 hours after synthesis. ANOVA test revealed a significant difference among SonoVue, synthesized contrast agent, and saline (p < 0.001). Although no significant difference was observed between SonoVue and the synthesized contrast agent, difference in echogenicity was observed between synthesized contrast agent and saline (p < 0.01). Conclusion: We could synthesize ultrasound contrast agents using an evaporation-drying-sonication method. On the basis of these results, many prospective types of research, such as anticancer drug delivery, gene delivery, including siRNA or microRNA, targeted molecular imaging, and targeted therapy can be performed.

The Application of an EU REACH Protocol to the Occupational Exposure Assessment of Methanol: Targeted Risk Assessment (메탄올 작업장 노출 평가에의 EU REACH 프로토콜 적용: Targeted Risk Assessment)

  • Ra, Jin-Sung;Song, Moon Hwan;Choe, Eun Kyung
    • Journal of Environmental Health Sciences
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    • v.47 no.5
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    • pp.432-445
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    • 2021
  • Background: The European Centre for Ecotoxicology and Toxicology of Chemicals' Targeted Risk Assessment (ECETOC TRA) tool has been recognized by EU REACH as a preferred approach for calculating worker health risks from chemicals. Objectives: The applicability of the ECETOC TRA to occupational exposure estimation from industrial uses of methanol was studied by inputting surveyed and varied parameters for TRA estimation as well as through comparison with measured data. Methods: Information on uses of methanol was collected from seven working environment monitoring reports along with the measured exposure data. Input parameters for TRA estimation such as operating conditions (OCs), risk management measures (RMMs) and process categories (PROCs) were surveyed. To compare with measured exposures, parameters from the surveyed conditions of ventilation but no use of respiratory protection were applied. Results: PROCs 4, 5, 8a, 10, and 15 were assigned to ten uses of methanol. The uses include as a solvent for manufacturing sun cream, surfactants, dyestuffs, films and adhesives. Methanol was also used as a component in a release agent, hardening media and mold wash for cast products as well as a component of hard-coating solution and a viscosity-controlling agent for manufacturing glass lenses. PROC 8a and PROC 10 of a cast product manufacturer without LEV (local exhaust ventilation) and general ventilation as well as no respiratory protection resulted in the highest exposure to methanol. Assuming the identical worst OCs and RMMs for all uses, exposures from PROC 5, 8a, and 10 were the same and the highest followed by PROC 4 and 15. The estimation resulted in higher exposures in nine uses except one use where measured exposure approximated exposures without RMMs. Conclusions: The role of ECETOC TRA as a conservative exposure assessment tool was confirmed by comparison with measured data. Moreover, it can guide which RMMs should be applied for the safe use of methanol.

Reinforcement Method to Enhance Adaptive Route Search for Efficient Real-Time Application Specific QoS Routing (Real-Time Application의 효과적인 QoS 라우팅을 위한 적응적 Route 선택 강화 방법)

  • Oh, Jae-Seuk;Bae, Sung-Il;Ahn, Jin-Ho;Sungh Kang
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.40 no.12
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    • pp.71-82
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    • 2003
  • In this paper, we present a new method to calculate reinforcement value in QoS routing algorithm targeted for real-time applications based on Ant algorithm to efficiently and effectively reinforce ant-like mobile agents to find the best route toward destination in a network regarding necessary QoS metrics. Simulation results show that the proposed method realizes QoS routing more efficiently and more adaptively than those of the existing method thereby providing better solutions for the best route selection for real-time application that has high priority on delay jitter and bandwidth.

Large-scale Synthesis of Uniform-sized Nanoparticles for Multifunctional Medical Applications

  • Hyeon, Taeg-Hwan
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.1-1
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    • 2011
  • We developed a new generalized synthetic procedure, called as "heat-up process," to produce uniform-sized nanocrystals of many transition metals and oxides without a size selection process. We were able to synthesize uniform magnetite nanocrystals as much as 1 kilogram-scale from the thermolysis of Fe-oleate complex. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group's recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized magnetite nanoparticles and their medical applications. Uniform ultrasmall iron oxide nanoparticles of <3 nm were synthesized by thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. These ultrasmall iron oxide nanoparticles exhibited good T1 contrast effect. In in vivo T1 weighted blood pool magnetic resonance imaging (MRI), iron oxide nanoparticles showed longer circulation time than commercial gadolinium complex, enabling high resolution imaging. We used 80 nm-sized ferrimagnetic iron oxide nanocrystals for T2 MRI contrast agent for tracking transplanted pancreatic islet cells and single-cell MR imaging. We reported on the fabrication of monodisperse magnetite nanoparticles immobilized with uniform pore-sized mesoporous silica spheres for simultaneous MRI, fluorescence imaging, and drug delivery. We synthesized hollow magnetite nanocapsules and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle.

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Cryo-EM as a powerful tool for drug discovery: recent structural based studies of SARS-CoV-2

  • Han‑ul Kim;Hyun Suk Jung
    • Applied Microscopy
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    • v.51
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    • pp.13.1-13.7
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    • 2021
  • The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.

Effect of TNF-$\alpha$ Gene Transfer to Respiratory Cancer Cell Lines on Sensitivity to Anticancer drugs (호흡기계암세포주에서 TNF-$\alpha$ 유전자의 이입이 항암제 감수성에 미치는 효과)

  • Mo, Eun-Kyung;Lee, Jae-Ho;Lee, Kye-Young;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Choi, Hyung-Seok
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.3
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    • pp.302-313
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    • 1995
  • Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

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