• Title/Summary/Keyword: 표적 항암제

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Application and therapeutic effects of sickle red blood cells for targeted cancer therapy (표적항암치료를 위한 겸형적혈구의 응용 및 치료 효과)

  • Choe, Se-woon
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.20 no.12
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    • pp.2395-2400
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    • 2016
  • Conventional drug carriers such as liposomes, nanoparticles, polymer micelles, polymeric conjugate and lipid microemulsion for cancer chemotherapy shield normal tissues from toxic drugs to treat cancer cells in tumors. However, inaccurate tumor targeting uncontrolled drug release from the carriers and unwanted accumulation in healthy sites can limit treatment efficacy with current conventional drug carriers with insufficient concentrations of drugs in the tumors and unexpected side effects as a result. Sickle red blood cells show natural tumor preferential accumulation without any manipulation due to the adhesive interaction between molecular receptors on the membrane surface and counter-receptor on endothelial cells. In addition, structural changes of microvascular in tumor sites enhances polymerization of sickle red blood cells. In this research, we examined the use of sickle red blood cells as a new drug carrier with novel tumor targeting and controlled release properties to quantify its therapeutic effects.

Application of sickle red blood cells for targeted cancer therapy (항암치료를 위한 겸형적혈구의 응용)

  • Choe, Se-woon
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2016.05a
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    • pp.715-717
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    • 2016
  • Conventional drug carriers such as liposomes, nanoparticles, polymer micelles, polymeric conjugate and lipid microemulsion for cancer chemotherapy shield normal tissues from toxic drugs to treat cancer cells in tumors. However, inaccurate tumor targeting uncontrolled drug release from the carriers and unwanted accumulation in healthy sites can limit treatment efficacy with current conventional drug carriers with insufficient concentrations of drugs in the tumors and unexpected side effects as a result. In this research, we examined the use of sickle red blood cells as a new drug carrier with novel tumor targeting and controlled release properties. Sickle red blood cells show natural tumor preferential accumulation without any manipulation and controlled drug release is possible using a hemolysis method with photosensitizers.

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Therapeutic efficacy of the photoactivated sickle cells as novel drug delivery vehicle (약물전달 시스템 개발을 위한 여기된 광감응제의 응용)

  • Choe, Se-woon
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2015.10a
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    • pp.958-960
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    • 2015
  • Sickle cells possess a unique combination of traits that may enable their use as models for novel synthetic tumor targeting controlled release drug carriers with the ability to treat disseminated tumors in advanced metastatic disease. In this study, we assess the ability of light-activated release sickle cells to enhance tumor delivery of the fluorescent dye calcein by delayed photolysis controlled release compared to free systemic administration of calcein. Sickle cells from mouse models of the disease were shown to preferentially accumulate in tumors compared to adjacent tissue, in 4T1 tumors in mice on a time scale about 12 hours. Sickle cells photosensitized with protoporphyrin IX achieved delayed release of 50% of contents 8-16 hours after photoactivation, which was deemed useful for in vivo delivery of cargo to tumors given the tumor accumulation time of the sickle cells. Sickle cells may be useful as a model for new synthetic drug carrier particles with delayed photolysis controlled release properties.

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Betulinic Acid Induces Apoptosis in Humam Mucoepidermoid Carcinoma Cells Through Regulating Specificity Protein 1 and Its Downstream Molecule, Survivin

  • Lee, Jung-Eun;Jung, Ji-Youn;Yoo, Hyun-Ju;Cho, Sung-Dae
    • Journal of Food Hygiene and Safety
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    • v.28 no.3
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    • pp.202-206
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    • 2013
  • High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

Effects of an Anti-cancer Drug, Tubastatin A, on the Growth and Development of Immature Oocytes in Mice (항암제 tubastatin A에 의한 생쥐 미성숙 난모세포의 성장과 발달에 미치는 효과)

  • Choi, Yun-Jung;Min, Gyesik
    • Journal of Life Science
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    • v.29 no.1
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    • pp.105-111
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    • 2019
  • In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.

Screening of Photosensitizer for Photodynamic Therapy (광역동 항암치료를 위한 광과민제 스크리닝 연구)

  • Kim, So-Young;Yoo, Gui-Jae;Park, Keun-Hyoung;Lim, Byung-Lak;Kim, Shi-Surk;Yom, Heng-Cherl;Chae, Hee-Jeong
    • KSBB Journal
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    • v.22 no.5
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    • pp.318-321
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    • 2007
  • Photodynamic therapy (PDT) is a targeted-tumor treatment system using a photosensitizer, light and oxygen to treat malignant tumor. We have investigated the cytotoxicity of 4 types of phthalocyanine derivative (silver phthalocyanine, iron (III) phthalocyanine, copper (II) phthalocyanine, nickel (II) phthalocyanine) against lung and breast cancers based on photodynamic therapy. As a result, phthalocyanine derivatives indicated a higher anticancer activity on a breast cancer cell line. Among the tested phthalocyanines, silver phthalocyanine (AgPc) showed a lower cytotoxicity against a normal cell line. In addition AgPc gave a good color characteristic when it is solubilized in water. Finally AgPc was selected as a potential antitumor agent for breast cancer.

Synergistic antitumor activity of ST1571 and camptothecin in human cancer cells (Camptothecin 에 의한 ST1571 의 항암 활성 증강)

  • Kim, Mi-Ju;Lee, Sang-Min;Bae, Jae-Ho;Chung, Byung-Seon;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.748-755
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    • 2007
  • The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

Characteristics of Cancer Stem Cells and Immune Checkpoint Inhibition (암줄기세포의 특성 및 면역관문억제)

  • Choi, Sang-Hun;Kim, Hyunggee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.499-508
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    • 2019
  • Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

신규 항암제 DA-125의 급성 및 특수독성 연구

  • 하광원;김부영;박정식;안병옥
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.37-37
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    • 1993
  • 1) 급성독성시험: 랫드와 마우스 공히 투여후 5~6일에 농도의존적의 강한 독성이 발현 되었으며 표적장기로는 소화기계, 임파계, 조혈기계 등으로 나타났다. 랫드에서의 반수 치사량은 암수 각각 771.9(505.6~1178.4)mg/kg과 479.8(302.7~760.4)mg/kg이었으며 마우스에서는 암수 각각 527.4(393.7~701.1)mg/kg과 463.0(308.8~694.2)mg/kg 이었다. 2) 유전독성: S. typhimurium을 이용한 복귀돌연변이시험, CHL세포를 이용한 염색체이상 시험, 마우스에서의 소핵시험결과 DA-125는 돌연변이 유발능을 갖는 것으로 나타났다. 3) 국소자극성: 혈관주위주사에 의한 피부자극성 시험결과 DA-125는 adriamycin의 3배 용량에서 궤양, 괴사등 유사한 병변이 유발되었으나, 병변회복은 adriamycin에 비해 빠른 것으로 나타났다. 또한 토끼에서의 안점막자극시험 결과에서 DA-125는 실제적으로 자극이 없는 것으로 나타났다.

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