• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.281-290
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• 2024

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

• Korean Journal of Materials Research
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• v.22 no.7
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• pp.362-367
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• 2012

Magnetite nanoparticles(NPs) have been the subject of much interest by researchers owing to their potential use as magnetic carriers in drug targeting and as a tumor treatment in cases of hyperthermia. However, magnetite nanoparticles with 10 nm in diameter easily aggregate and thus create large secondary particles. To disperse magnetite nanoparticles, this study proposes the infiltration of magnetite nanoparticles into hybrid silica aerogels. The feasible dispersion of magnetite is necessary to target tumor cells and to treat hyperthermia. Magnetite NPs have been synthesized by coprecipitation, hydrothermal and thermal decomposition methods. In particular, monodisperse magnetite NPs are known to be produced by the thermal decomposition of iron oleate. In this study, we thermally decomposed iron acetylacetonate in the presence of oleic acid, oleylamine and 1,2 hexadecanediol. We also attempted to disperse magnetite NPs within a mesoporous aerogels. Methyltriethoxysilicate(MTEOS)-based hybrid silica aerogels were synthesized by a supercritical drying method. To incorporate the magnetite nanoparticles into the hybrid aerogels, we devised two methods: adding the synthesized aerogel into a magnetite precursor solution followed by nucleation and crystal growth within the pores of the aerogels, and the infiltration of magnetite nanoparticles synthesized beforehand into aerogel matrices by immersing the aerogels in a magnetite nanoparticle colloid solution. An analysis using a vibrating sample magnetometer showed that approximately 20% of the magnetite nanoparticles were well dispersed in the aerogels. The composite samples showed that heating under an inductive magnetic field to a temperature of $45^{\circ}C$ is possible.

• Polymer(Korea)
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• v.26 no.5
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• pp.691-700
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• 2002

Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.89-100
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• 2019

In our previous studies, we developed a ¹⁸F-labeled TSPO-binding ligand, named [¹⁸F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

• The Korean Journal of Nuclear Medicine
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• v.38 no.3
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• pp.253-258
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• 2004

Purpose: Chitosan has been studied as a non-viral gene delivery vector, drug delivery carrier, metal chelator, food additive, and radiopharmaceutical, among other things. Recently, galactose-graft chitosan was studied as a non-viral gene and drug delivery vector to target hepatocytes. The aim of this study was to investigate the usefulness of nuclear imaging for in vivo evaluation of targeting the hepatocyte by galactose grafting. Methods and Materials: Galactosyl methylated chitosan (GMC) was produced by methylation to lactobionic acid coupled chitosan. Cytotoxicity of $^{99m}Tc$-GMC was determined by MTT assay. Rabbits were injected via their auricular vein with $^{99m}Tc$-GMC and $^{99m}Tc$-methylated chitosan (MC), the latter of which does not contain a galactose group, and images were acquired with a gamma camera equipped with a parallel hole collimator. The composition of the galactose group in galactosylated chitosan (GC), as well as the tri-, di-, or mono-methylation of GMC, was confirmed by NMR spectroscopy. Results: The results of MTT assay indicated that $^{99m}Tc$-GMC was non-toxic. $^{99m}Tc$-GMC specifically accumulated in the liver within 10 minutes of injection and maintained high hepatic uptake. In contrast, $^{99m}Tc$-MC showed faint liver uptake. $^{99m}Tc$-GMC scintigraphy of rabbits showed that the galactose ligand principally targeted the liver while the chitosan functionalities led to excretion through the urinary system. Conclusion: Bioconjugation with a specific ligand endows some degree of targetability to an administered molecule or drug, as in the case of galactose for hepatocyte in vivo, and evaluating said targetabililty is a clear example of the great benefit proffered by nuclear imaging.

• The Korean Journal of Pain
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• v.31 no.4
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• pp.244-252
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• 2018

C-arm fluoroscopy is useful equipment in interventional pain management because it helps to guide correct needle targeting for the accurate injection and drug delivery. However, due to increased use of C-arm fluoroscopy in various pain procedures, the risk of radiation exposure is a significant concern for pain physicians. The harmful biological effects of ionizing radiation on the human body are well known. It is therefore necessary to strive to reduce radiation exposure. Lead aprons with thyroid shields are the most fundamental radiation protective devices for interventional procedures, and are very effective. However, the operator's radiation safety cannot be guaranteed because pain physicians seem to lack sufficient interest, knowledge, and awareness about radiation safety. Also, inappropriate care and use of radiation protective devices may result in a higher risk of radiation exposure. The purpose of this article was to review the literature on radiation safety with a focus on lead aprons and thyroid shields and present recommendations related to those devices during C-arm fluoroscopic-guided interventions by pain physicians.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5311-5316
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• 2014

Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

• Applied Chemistry for Engineering
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• v.27 no.6
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• pp.599-605
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• 2016

Recently, photodynamic and photothermal therapies have received increasing attention as an effective cancer treatment. In this study, a gold nanorod (AuNR) colloidal solution was synthesized as a hyperthermia agent for photothermal therapy and also modified with photosensitizer (PS) for photodynamic therapy. PEG (polyethylene glycol) and FA (folic acid) ligand were also introduced into AuNR for the long circulation in human body and efficient targeting of cancer cells, respectively and AuNRs were modified with FA-PEG and poly-${\beta}$-benzyl-L-aspartate (PBLA) block copolymers through a 3,4-dihydroxy hydrocinnamic acid (HCA) linker. A series of AuNRs with various aspect ratios were synthesized by controlling the feeding ratio of $AgNO_3$. The physicochemical property and morphology of synthesized AuNR100 and FA-PEG-$P(Asp)_{50}$-HCA-AuNR100 were analyzed by UV-visible spectrophotometer, $^1H$ NMR, XPS measurements, TEM. The surface modified AuNR carrier with biocompatibility could be applied for the effective diagnosis as well tumor phototherapy.

• The Korean Journal of Nuclear Medicine
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• v.39 no.5
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• pp.278-283
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• 2005

Purpose: In prior study, we synthesized $^{99m}Tc$-galactosylated chitosan (GC) and performed in vivo biodistribution study, showed specific targeting to hepatocyte. The aim of this study is to evaluate the labeling efficiency and cytotoxicity of modified galactosylated chitosan compounds, galactosyl methylated chitosan (GMC) and HYNIC-galactosylated chitosan (GCH). Materials and Methods: GC, GMC and GCH were synthesized and radiolabeled with $^{99m}Tc$. Then, they were incubated for 6 hours at room temperature and human serum at $37^{\circ}C$. Labeling efficiencies were determined at 15, 30 m, 1, 2, 3 and 6 h after radiolabeling. To evaluate cytotoxicity, MTT assay was performed in HeLa and HepG2 cells. Results: In comparison with them of $^{99m}Tc$-GC labeling efficiencies of $^{99m}Tc$-GMC were significantly improved (100, 97 and 89%) in acetone and 96.3, 95.8 and 75.6% in saline at 15 m, 1 and 6 h, respectively). Moreover, $^{99m}Tc$-GCH showed more improved labeling efficiencies (>95% in acetone and human serum and >90% in saline at 6 h). In MTT assay, cytotoxicity was very low and not different from that of controls. Conclusion: These results represent that these compounds are radiochemically compatible radiopharmaceuticals, can be used in hepatocyte specific imaging study and in vivo gene or drug delivery monitoring.