• Archives of Pharmacal Research
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• 제29권7호
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• pp.605-616
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• 2006

A wide variety of drugs and endogenous bioactive amines are organic cations (OCs). Approximately 40% of all conventional drugs on the market are OCs. Thus, the transport of xenobiotics or endogenous OCs in the body has been a subject of considerable interest, since the discovery and cloning of a family of OC transporters, referred to as organic cation transporter (OCTs), and a new subfamily of OCTs, OCTNs, leading to the functional characterization of these transporters in various systems including oocytes and some cell lines. Organic cation transporters are critical in drug absorption, targeting, and disposition of a drug. In this review, the recent advances in the characterization of organic cation transporters and their distribution in the small intestine are discussed. The results of the in vitro transport studies of various OCs in the small intestine using techniques such as isolated brush-border membrane vesicles, Ussing chamber systems and Caco-2 cells are discussed, and in vivo knock-out animal studies are summarized. Such information is essential for predicting pharmacokinetics and pharmacodynamics and in the design and development of new cationic drugs. An understanding of the mechanisms that control the intestinal transport of OCs will clearly aid achieving desirable clinical outcomes.

• Molecules and Cells
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• 제42권11호
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• pp.804-809
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• 2019

Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations.

• Journal of Dairy Science and Biotechnology
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• 제37권1호
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• pp.69-80
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• 2019

The elderly often experience difficulty while eating; this can include physical problems, such as chewing and swallowing. Furthermore, their salt intake can be high due to a diminished sense of taste and smell. This can result in a reduction in calorie intake and subsequent malnourishment. Currently, the number of food products available in the market that are targeted specifically at the older population is very low. Development of nutritional supplement-based foods for the elderly is expected to reduce these dietary problems and therefore prevent nutritional deficiencies within this population. Milk and other dairy products are excellent sources of nutrition in terms of both nutrient content and absorption rates. Dairy products have been consumed around the world for centuries, and therefore represent an excellent food source for the elderly. In addition, use of milk-derived ingredients, such as casein and calcium, will enable the development of a variety of food products and supplements targeted at this specific age group. In the future, it is expected that milk and other dairy products will be used to develop a variety of nutritious food items for the elderly in the domestic food market.

• Journal of Gastric Cancer
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• 제19권2호
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• pp.148-156
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• 2019

Esophagogastric junction (EGJ) cancer is a solid tumor entity with rapidly increasing incidence in the Western countries. Given the high proportion of advanced cancers in the West, treatment strategies routinely employed include surgery and chemotherapy perioperatively, and chemoradiation in neoadjuvant settings. Neoadjuvant chemoradiation and perioperative chemotherapy are mostly performed in esophageal cancer that extends to the EGJ and gastric as well as EGJ cancers, respectively. Recent trials have tried to combine both strategies in a perioperative context, which might have beneficial outcomes, especially in patients with EGJ cancer. However, it is difficult to recruit patients for trials, exclusively for EGJ cancers; therefore, the results have to be carefully reviewed before establishing a standard protocol. Trastuzumab was the first drug for targeted therapy that was positively evaluated for this tumor entity, and there are several ongoing trials investigating more targeted drugs in order to customize effective therapies based on tissue characteristics. The current study reviews the multimodal treatment concept for EGJ cancers in the West and summarizes the latest reports.

• Journal of Korean Neurosurgical Society
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• 제62권1호
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• pp.10-26
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• 2019

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• 제61권12호
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• pp.637-643
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• 2018

Radioimmunotherapy (RIT) is a therapy that takes advantage of the "cross-fire" effect of emitted radiation by radionuclides conjugated to tumor-directed monoclonal antibodies (mAb) (including those fragments) or peptides. While RIT has been successfully employed for the treatment of lymphoma, mostly with radiolabeled antibodies against CD20 [$^{90}yttrium$ ($^{90}Y$)-ibritumomab tiuxetan; $Zevalin^{(R)}$ and $^{131}iodine$ ($^{131}I)-tositumomab$; $Bexxar^{(R)}$], its use in solid tumors is more challenging, so far. Immuno-PET, a tool for tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and guide mAb-based therapy. RIT in solid tumors including head and neck cancer may be an alternative treatment with advances in various biological, chemical, and treatment procedures, and it may help to reduce unnecessary exposure and enhance the therapeutic efficacy. Also, immuno-PET based on RIT might play an important role in cancer staging, in patients or targets selection of targeted therapeutics and in monitoring the response of targeted therapeutics as precision medicine. In this review, fundamentals of RIT/immune-PET and current knowledge of the preclinical/clinical trials in RIT for solid tumor including head and neck cancer are reviewed.

• 한국동물생명공학회지
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• 제35권4호
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• pp.323-328
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• 2020

Direct injection of genome editing tools such as CRISPR/Cas9 system into developing embryos has been widely used to generate genetically engineered pigs. The approach allows us to produce pigs carrying targeted modifications at high efficiency without having to apply somatic cell nuclear transfer. However, the targeted modifications during embryogenesis often result in mosaicism, which causes issues in phenotyping founder animals and establishing a group of pigs carrying intended modifications. This study was aimed to establish a genomic PCR and sequencing system of a single blastomere in the four-cell embryos to detect potential mosaicism. We performed genomic PCR in four individual blastomeres from four-cell embryos. We successfully amplified target genomic region from single blastomeres of 4-cell stage embryo by PCR. Sanger sequencing of the PCR amplicons obtained from the blastomeres suggested that PCR-based genotyping of single blastomere was a feasible method to determine mutation type generated by genome editing technology such as CRISPR/Cas9 in early stage embryos. In conclusion, we successfully genotyped single blastomeres in a single 4-cell stage embryo to detect potential mosaicism in porcine embryos. Our approach offers a simple platform that can be used to screen the prevalence of mosaicism from designed CRISPR/Cas9 systems.

• 대한두경부종양학회지
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• 제37권2호
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• pp.11-17
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• 2021

Head and neck cancer is the 6^th most frequently diagnosed solid tumor in the world. Alcohol consumption, smoking, and HPV infection are associated with the incidence of head and neck squamous cell carcinoma (HNSCC). Although a multidisciplinary approach is a key strategy for the treatment of locally advanced HNSCC, systemic therapy is the mainstream of recurrent or metastatic HNSCC treatment. Stage IV HNSCC has a relatively poor prognosis with median overall survival of around one year. There have been many clinical trials to investigate the efficacy of target agents in the treatment of HNSCC. In the HPV-negative HNSCC, TP53 and CDKN2A are the most commonly mutated genes. In the HPV-positive HNSCC, the PI3K pathway is frequently altered. EGFR, PI3K, cell cycle pathway, MET, HRAS, and IL6/JAK/STAT pathway are explored targets in HNSCC. In this study, we review the target pathways and agents under research. We also introduce here umbrella trials of recurrent or metastatic HNSCC conducted by the Korea Cancer Study Group. The combination of target agents with immune checkpoint inhibitors or cytotoxic chemotherapies would be a future step in the precision medicine of HNSCC treatment.

• 대한방사선기술학회지:방사선기술과학
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• 제45권5호
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• pp.433-438
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• 2022

Targeted radionuclides treatment (TRT) requires the establishment of treatment plans that consider various factors, such as the type of radionuclides, target organs, and administration methods. For this reason, in this study, the absorption dose of a single cell was analyzed according to the type of radioisotope used to treat target radionuclides. In this study, a simulation was performed on beta rays used in the treatment of target radionuclides at the cell level using MCNPX (ver. 2.5.0). First, according to the calculation formula, the beam path according to the type of radioisotope for treatment was calculated. Second, the amount of self-radiation by beta rays emitted from cell diameters of 5 ㎛ and 10 ㎛ cell nuclei was evaluated. As a result, it showed a high range proportional to the maximum energy of the beta-ray, and the highest self-dose distribution from 177 Lu radiation sources among therapeutic radioisotopes. This was analyzed as a result that is inversely proportional to the maximum energy of the beta-ray, and it suggests that the selection of a nuclide considering the range of the beta-ray is necessary in the treatment of target radionuclides in the future.

• Molecules and Cells
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• 제45권9호
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• pp.631-639
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• 2022

Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.