• Title/Summary/Keyword: theragnosis

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Development of Drugs and Technology for Radiation Theragnosis

  • Jeong, Hwan-Jeong;Lee, Byung Chul;Ahn, Byeong-Cheol;Kang, Keon Wook
    • Nuclear Engineering and Technology
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    • v.48 no.3
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    • pp.597-607
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    • 2016
  • Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

Novel function of stabilin-2 in myoblast fusion: the recognition of extracellular phosphatidylserine as a "fuse-me" signal

  • Kim, Go-Woon;Park, Seung-Yoon;Kim, In-San
    • BMB Reports
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    • v.49 no.6
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    • pp.303-304
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    • 2016
  • Myoblast fusion is important for skeletal muscle formation. Even though the knowledge of myoblast fusion mechanism has accumulated over the years, the initial signal of fusion is yet to be elucidated. Our study reveals the novel function of a phosphatidylserine (PS) receptor, stabilin-2 (Stab2), in the modulation of myoblast fusion, through the recognition of PS exposed on myoblasts. During differentiation of myoblasts, Stab2 expression is higher than other PS receptors and is controlled by calcineurin/NFAT signaling on myoblasts. The forced expression of Stab2 results in an increase in myoblast fusion; genetic ablation of Stab2 in mice causes a reduction in muscle size, as a result of impaired myoblast fusion. After muscle injury, muscle regeneration is impaired in Stab2-deficient mice, resulting in small myofibers with fewer nuclei, which is due to reduction of fusion rather than defection of myoblast differentiation. The fusion-promoting role of Stab2 is dependent on its PS-binding motif, and the blocking of PS-Stab2 binding impairs cell-cell fusion on myoblasts. Given our previous finding that Stab2 recognizes PS exposed on apoptotic cells for sensing as an "eat-me" signal, we propose that PS-Stab2 binding is required for sensing of a "fuse-me" signal as the initial signal of myoblast fusion.

Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells

  • Shin, Miyoung;Yang, Eun Gyeong;Song, Hyun Kyu;Jeon, Hyesung
    • BMB Reports
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    • v.48 no.6
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    • pp.342-347
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    • 2015
  • The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting (나노의학: 나노물질을 이용한 약물전달시스템과 나노입자의 표적화)

  • Youn, Hye-Won;Kang, Keon-Wook;Chung, June-Key;Lee, Dong-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.5
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    • pp.337-346
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    • 2008
  • Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development.

N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code

  • Nguyen, Kha The;Ju, Shinyeong;Kim, Sang-Yoon;Lee, Chang-Seok;Lee, Cheolju;Hwang, Cheol-Sang
    • Molecules and Cells
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    • v.45 no.3
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    • pp.158-167
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    • 2022
  • Ubiquitin (Ub) is post-translationally modified by Ub itself or Ub-like proteins, phosphorylation, and acetylation, among others, which elicits a variety of Ub topologies and cellular functions. However, N-terminal (Nt) modifications of Ub remain unknown, except the linear head-to-tail ubiquitylation via Nt-Met. Here, using the yeast Saccharomyces cerevisiae and an Nt-arginylated Ub-specific antibody, we found that the detectable level of Ub undergoes Nt-Met excision, Nt-deamination, and Nt-arginylation. The resulting Nt-arginylated Ub and its conjugated proteins are upregulated in the stationary-growth phase or by oxidative stress. We further proved the existence of Nt-arginylated Ub in vivo and identified Nt-arginylated Ub-protein conjugates using stable isotope labeling by amino acids in cell culture (SILAC)-based tandem mass spectrometry. In silico structural modeling of Nt-arginylated Ub predicted that Nt-Arg flexibly protrudes from the surface of the Ub, thereby most likely providing a docking site for the factors that recognize it. Collectively, these results reveal unprecedented Nt-arginylated Ub and the pathway by which it is produced, which greatly expands the known complexity of the Ub code.

Measurements of $T_1$-and $T_2$-relaxation Time Changes According to the Morphological Characteristics of Gold Nanoparticles (GNPs) (금 나노 입자의 형태적 특성에 따른 $T_1$, $T_2$ 이완 시간의 변화 측정)

  • Jang, M.Y.;Han, Y.H.;Mun, C.W.
    • Investigative Magnetic Resonance Imaging
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    • v.15 no.1
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    • pp.48-56
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    • 2011
  • Purpose : The aim of this study is to measure the typical MR variables such as $T_1$- and $T_2$-relaxation times according to morphological characteristics of gold nanopartides as a preliminary study to perform theragnosis using local heating by gold nanopartides. Materials and Methods : Two types of gold nanoparticles were used. Spheres were synthesized by various methods and stirring speed. Rods were synthesized by adding various concentrations of sphere nanopartides. Gold nanopartides were mixed with 2% agarose gel at 1:1 ratio and then signals were acquired using a 1.5T MRI. For the measurements of $T_1$-and $T_2$-relaxation times, TR and TE were varied, respectively. The results were acquired through $T_1$ and $T_2$ curves based on the intensities of MR image using self-developed software. And Statistical analysis was performed. Results : $T_1$ times were measured 1.86 sec and 2.08 sec for sphere and rod, respectively. On the other hands, $T_2$ times were measured 57 ms and 35.45 ms for sphere and rod. Conclusion : The changes of the MR variables according to the morphological characteristics of the gold nanopartides were confirmed. Optimal MR imaging conditions can be obtained by choosing proper TR and TE according to the type of nanoparticles.

Neuropeptidomics: Mass Spectrometry-Based Identification and Quantitation of Neuropeptides

  • Lee, Ji Eun
    • Genomics & Informatics
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    • v.14 no.1
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    • pp.12-19
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    • 2016
  • Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides.

One-pot Synthesis of Multifunctional Mn3O4/mesoporous Silica Core/shell Nanoparticles for Biomedical Applications

  • Lee, Dong Jun;Lee, Nohyun;Lee, Ji Eun
    • Applied Chemistry for Engineering
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    • v.33 no.1
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    • pp.113-118
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    • 2022
  • Multifunctional nanomaterials based on mesoporous silica nanoparticles (MSN) and metal oxide nanocrystals are among the most promising materials for theragnosis because of their ease of modification and high biocompatibility. However, the preparation of multifunctional nanoparticles requires time-consuming multistep processes. Herein, we report a simple one-pot synthesis of multifunctional Mn3O4/mesoporous silica core/shell nanoparticles (Mn3O4@mSiO2) involving the temporal separation of core formation and shell growth. This simple procedure greatly reduces the time and effort required to prepare multifunctional nanoparticles. Despite the simplicity of the process, the properties of nanoparticles are not markedly different from those of core/shell nanoparticles synthesized by a previously reported multistep process. The Mn3O4@mSiO2 nanoparticles are biocompatible and have potential for use in optical imaging and magnetic resonance imaging.