• BMB Reports
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• 제47권3호
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• pp.149-157
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• 2014

The recent dramatic improvements in high-resolution mass spectrometry (MS) have revolutionized the speed and scope of proteomic studies. Conventional MS-based proteomics methodologies allow global protein profiling based on expression levels. Although these techniques are promising, there are numerous biological activities yet to be unveiled, such as the dynamic regulation of enzyme activity. Chemical proteomics is an emerging field that extends these types proteomic profiling. In particular, activity-based protein profiling (ABPP) utilizes small-molecule probes to monitor enzyme activity directly in living intact subjects. In this mini-review, we summarize the unique roles of smallmolecule probes in proteomics studies and highlight some recent examples in which this principle has been applied.

• The Plant Pathology Journal
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• 제22권3호
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• pp.235-238
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• 2006

Chrysanthemum stunt viroid (CSVd) induced systemic symptoms on chrysanthemum. We detected small RNAs of approximately 22 nucleotides with sequence specificity to CSVd in chrysanthemum infected with CSVd: an indication of the presence of RNA silencing. Regardless of symptom differences associated with CSVd, the small RNAs distributed similarly in amount. Small RNAs were detected with partial-length or full-length probes, indicating that they are not restricted to specific viroid regions but likely representing most of the viroid molecule.

• Nuclear Medicine and Molecular Imaging
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• 제42권3호
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• pp.185-191
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• 2008

While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

• 대한방사성의약품학회지
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• 제5권2호
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• pp.145-151
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• 2019

Fluorine-18 is considered to be the radionuclide of choice for positron emission tomography (PET). Thus, the development of small molecule-based radiopharmaceuticals for use in diagnostic imaging relies heavily on efficient radiofluorination techniques. Until the early 2000s, diaryliodonium salts and aryliodonium ylides were widely employed as labeling precursors to yield aromatic PET radiotracers with cyclotron-produced [¹⁸F]fluoride ion. Rapid recent progress in the development of efficient borylation methods has led to a paradigm shift in ¹⁸F-labeling methods. In addition, deoxyfluorination has attracted a great deal of interest as an alternative approach to aryl ring activation with ¹⁸F^-. In this review, methods for radiolabel development are discussed with a specific focus on the progress made in the last 5 years. Other interesting ¹⁸F-based protocols are also briefly introduced. New methods for exploiting ¹⁸F^- are expected to increase the number of ¹⁸F-labeling methods, to allow applications in a range of chemical environments.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.113-118
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• 2022

Gadolinium neutron capture therapy (Gd-NCT) is a precision radiation therapy that kills cancer cells using the neutron capture reaction that occurs when ¹⁵⁷Gd hits thermal neutrons. ¹⁵⁷Gd has the highest thermal neutron capture cross section of 254,000 barns among stable isotopes in the periodic table. Another stable isotope, ¹⁵⁵Gd, also has a high thermal neutron trapping area (~ 60,700 barns), so gadolinium that exists in nature can be used as a Gd-NCT drug. Gd-NCT is a mixed kinetic energy of low-energy and high-energy ionizing particles, which can be uniformly distributed throughout the tumor tissue, thereby solving the disadvantage of heterogeneous dose distribution in tumor tissue. The Gd complexes of small-sized molecule are widely used as contrast agents for magnetic resonance imaging (MRI) in clinical practice. Therefore, these compounds can be used not only for diagnosis but also therapy when considering the concept of Gd-NCT. This multifunctional trial can look forward to new medical advance into NCT clinical practices. In this review, we introduce gadolinium compounds suitable for Gd-NCT and describe the necessity of image guided Gd-NCT.

• IMMUNE NETWORK
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• 제1권1호
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• pp.7-13
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• 2001

Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

• Molecules and Cells
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• 제37권6호
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• pp.449-456
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• 2014

The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23b-transfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.