• Title/Summary/Keyword: Drug targeting

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Molecular Nuclear imaging of Angiogenesis (혈관신생 분자핵의학 영상)

  • Lee, Kyung-Han
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.171-174
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    • 2004
  • Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.

Factors Affecting Suicidal Ideation and Suicidal Attempts in Adolescents who have been Bullied (폭력 경험이 있는 청소년의 자살 생각 및 자살 시도에 영향을 미치는 요인)

  • Kim, Ji-In;Boo, Yun Jeong;Yi, Jee Seon
    • Journal of the Korean Society of School Health
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    • v.28 no.2
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    • pp.89-98
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    • 2015
  • Purpose: The purpose of this study was to determine the factors that influence suicidal ideation and suicidal attempts of adolescents who had been bullied. Methods: This study used data extracted from Korea Youth Risk Behavior Web-Based Survey of 2014. The data of 1,926 adolescents, in total, who had experienced violence were included in the analysis, The analysis was done using SPSS/WIN. Results: The adolescents with an experience of being bullied were more likely to engage in suicidal ideation and suicidal attempts than the average teenagers in Korea. In addition, suicidal thoughts were affected by gender, experience of habitual drug use, subjective happiness, as well as sadness and despair. Suicidal attempts were influenced by gender, grade, smoking experience, experience of habitual drug use, size of the city of residence, subjective happiness, sadness and hopelessness, existence of people to get counseling, and habit of walking for 10 minutes every day. Conclusion: More attention should be given to the suicidal risk of adolescents having experienced violence. Further studies are required to develop an intervention program for suicide prevention targeting adolescents who have experienced violence and assess the program's effectiveness.

Cell Surface Antigen Display for Neuronal Differentiation-Specific Tracking

  • Kim, Sang Chul;Lee, Eun-Hye;Yu, Ji Hea;Kim, Sang-Mi;Nam, Bae-Geun;Chung, Hee Yong;Kim, Yeon-Soo;Cho, Sung-Rae;Park, Chang-Hwan
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.78-84
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    • 2019
  • Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5' UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.

Discovery of Anticancer Activity of Amentoflavone on Esophageal Squamous Cell Carcinoma: Bioinformatics, Structure-Based Virtual Screening, and Biological Evaluation

  • Chen, Lei;Fang, Bo;Qiao, Liman;Zheng, Yihui
    • Journal of Microbiology and Biotechnology
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    • v.32 no.6
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    • pp.718-729
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    • 2022
  • Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

Clinical Applications of a Non-ablative Fractional Dual Laser (1550/1927 nm)

  • Chang, Ho Sun;Lim, Nam Kyu
    • Medical Lasers
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    • v.9 no.2
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    • pp.110-118
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    • 2020
  • The non-ablative fractional dual laser is equipped with two types of lasers, 1550 nm and 1927 nm in one device, and was approved by the United States Food and Drug Administration in 2013. The advantages of the non-ablative fractional laser (NAFL) include fewer side effects such as erythema, edema, post-laser pigmentation, and scab formation. Thus, the NAFL is preferred by both practitioners and consumers because it is convenient and safe for use. The 1550 nm erbium glass and 1927 nm thulium lasers are representative NAFLs that have been developed separately and are often used as a single-wavelength laser with proven clinical efficacy in various indications. The 1550 nm wavelength laser penetrates the dermis layer and the 1927 nm wavelength laser is effective for epidermal lesions. Therefore, targeting the skin layer can be easily achieved with both the 1550 and 1927 nm lasers, respectively, or in combination. Clinically, the 1550 nm laser is effective in the treatment of mild to moderate sagging and wrinkles, scars, and resurfacing. The 1927 nm laser improves skin texture and treats skin pigmentation and wounds. It can also be used for drug delivery. The selection and utilization rate of NAFL has been increasing in recent times, due to changes in lifestyle patterns and the need for beauty treatments with fewer side effects and short downtime. In this study, we present a plan for safe and effective laser therapy through a review of literature. Clinical applications of the multifunctional NAFL are also described.

Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

  • Hyunji Choi;Moonkyung Kang;Kee-Ho Lee;Yeon-Soo Kim
    • BMB Reports
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    • v.56 no.11
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    • pp.612-617
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    • 2023
  • Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation

  • Hyoeun Jeon;Jungeun Yu;Jung Me Hwang;Hye-Won Park;Jiyeon Yu;Zee-Won Lee;Taesoo Kim;Jaerang Rho
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.43.1-43.12
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    • 2022
  • Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Development of PLGA Nanoparticles for Astrocyte-specific Delivery of Gene Therapy: A Review (별아교세포 선택적 유전자 치료전달을 위한 PLGA 나노입자 개발)

  • Shin, Hyo Jung;Lee, Ka Young;Kwon, Kisang;Kwon, O-Yu;Kim, Dong Woon
    • Journal of Life Science
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    • v.31 no.9
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    • pp.849-855
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    • 2021
  • Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

The Impact of Outpatient Coinsurance Rate Increase on Outpatient Healthcare Service Utilization in Tertiary and General Hospital (외래 본인부담률 인상이 상급종합병원과 종합병원 외래 의료이용에 미친 영향)

  • Kim, Hyo-Jeong;Kim, Young-Hoon;Kim, Han-Sung;Woo, Jung-Sik;Oh, Su-Jin
    • Health Policy and Management
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    • v.23 no.1
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    • pp.19-34
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    • 2013
  • Background: The study describes the changes resulted from imposition on tertiary hospital outpatient coinsurance rate rise policy and in tertiary or general hospital drug coverage rise policy on healthcare service utilization. Methods: Accordingly, the hypothesis about outpatient healthcare utilization after rise policy in outpatient coinsurance rate and drug coverage was established, using interrupted time-series analysis and segmented regression analysis to test the hypothesis. 5-year analysis period (2007. 3-2012. 3) from the outset year was designated, the data about most common 10 high-ranking of the main diseases targeting visiting patient from age of 6 to 64 were collected. Results: The summary on the major research is followed. First, the medical expense and duration of treatment tends to be increased in case of imposition about rise policy in outpatient coinsurance rate in the tertiary hospital under the interrupted time-series analysis. It showed temporary increase and slow down on account of influenza A even after the policy enforcement. In segmented regression analysis, duration of visit and medical expense in the tertiary hospital increased temporally right after the policy implementation and the decreased rapidly depends on period. Both rise and fall is statistically significant. The second, In case of tertiary or general hospital outpatient drug coverage rise policy, all of the tertiary hospital healthcare service utilization variables by the interrupted time-series analysis, drug coverage policy in the general hospital deeply declined according to decreasing trend before policy implementation. The third, in case of segmented regression analysis, the visit duration and medical expense statistically declined right after the policy implementation in both the tertiary and general hospital. Meanwhile, administration day was statistically meaningful only for the decrease right after the policy implementation. Otherwise, general hospital changes are not statistically meaningful. And the medicine cost was statistically, meaningfully decreased after the increase in drug coverage. Conclusion: Finally, the result demonstrated according to the analysis is only 1 hypothesis is denied, the other 2 are partially supported. Then, tertiary hospital outpatient coinsurance rate increase policy comparatively makes decrease effect on long-term healthcare utilization, and tertiary or general hospital outpatient drug coverage policy showed partially short-term effect is assured.

Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells

  • Mellatyar, Hassan;Talaei, Sona;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.5
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    • pp.2453-2457
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    • 2016
  • Background: Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. Materials and Methods: The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. Results: Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. Conclusions: PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent.