• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.97-102
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• 2002

Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.31-38
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• 2023

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.525-533
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• 1997

연구배경 : 수술적 절제가 불가능한 폐암환자에서 복합화학요법의 역할이 최근 증대되고 있으나 아직 가장 이상적인 복합화학요법은 확립되지 않고 있다. 두 종류 이상의 항암제를 복합투여시 약제간의 상호작용에 의해 항암효과의 상승 혹은 억제를 보일 수 있으나 이를 예측하기가 어려웠다. 본 연구에서는 MTT 검사를 이용하여 두 약제를 여러 농도에서 복합투여후 살해능의 변화를 관찰하였다. 방 법 : 사람의 폐선암세포인 PC-14를 이용하여 cisplatin, mitomycin C, adriamycin 및 etoposide를 여러 농도에서 단독 또는 두 약제를 복합투여하여 항암효과의 변화를 MTT 검사로 측정하고 두 약제 복합투여시의 상호 작용의 결과를 이원배치법을 이용한 Anova분석을 이용하여 측정하였다. 결 과 : 위의 네종류의 약제는 단독투여시 농도에 비례하는 암세포살해능을 보였고 두 약제를 복합투여시 모든 조합에서 암세포살해능의 상승효과를 보였으며 특히 mitomycin C 와 cisplatin 및 adriamycin과 cisplatin을 복합투여시 상승효과가 강하게 나타났다. 결 론 : 위의 결과로 비소세포폐암의 복합화학요법시 mitomycin C와 cisplatin 혹은 adriamycin과 cisplatin을 같이 사용할 경우 항암효과의 극대화를 얻을 수 있으리라 기대된다. 나아가 이번 연구의 디자인은 복합항암화학요법을 필요로 하는 모든 종류의 암에 적용되어 최대항암효과를 얻을 수 있는 약제선정에 도움의 될 수 있으리라 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3023-3028
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• 2013

Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

• 셀메드
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• 제2권2호
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• pp.18.1-18.16
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• 2012

An oncology-specific database called OncoRx (http://bit.ly/cancerRx) was previously set up in cyberspace to aid clinicians in identifying interactions of anticancer drugs (ACDs) and chemotherapy regimens with traditional Chinese medicines (TCMs) and complementary and alternative medicines (CAMs). Since then, users have requested the drug-CAM interactions (DCIs) of 5 specific CAMs (cranberry, melatonin, co-enzyme Q10, huachansu, reishi mushroom) to be updated in the database. Pharmacokinetic properties (metabolism, enzyme induction/inhibition, elimination), TCM properties and DCIs of each CAM were collated with 117 ACDs using 9 hardcopy compendia and online databases as resources. Additionally, individual ACDs and CAMs were used as keywords for PubMed searches in combination with the terms 'anticancer drugs', 'drug interactions', 'herb-drug/drug-herb interactions', 'pharmacokinetic interactions' and 'pharmacodynamic interactions'. DCI parameters consisted of interaction effects, evidence summaries, proposed management plans and alternative non-interacting CAMs, together with relevant citations and update dates of the DCIs. OncoRx is also used as a case to introduce the "Four Pharmaco-cybernetic Maxims" of quality, quantity, relationship and manner to developers of digital healthcare tools. Its role in Hayne's "5S" hierarchy of research evidence is also presented. OncoRx is meant to complement existing DCI resources for clinicians and alternative medicine practitioners as an additional drug information resource that provides evidence-based DCI information for ACD-CAM interactions.

• Nutrition Research and Practice
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• 제15권1호
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• pp.12-25
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• 2021

BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.139-150
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• 2017

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

• Journal of Microbiology and Biotechnology
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• 제33권7호
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• pp.849-856
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• 2023

Short-chain fatty acids (SCFAs), such as butyrate, propionate, and acetate produced by the gut microbiota have been implicated in physiological responses (defense mechanisms, immune responses, and cell metabolism) in the human body. In several types of cancers, SCFAs, especially butyrate, suppress tumor growth and cancer cell metastasis via the regulation of the cell cycle, autophagy, cancer-related signaling pathways, and cancer cell metabolism. In addition, combination treatment with SCFAs and anticancer drugs exhibits synergistic effects, increasing anticancer treatment efficiency and attenuating anticancer drug resistance. Therefore, in this review, we point out the importance of SCFAs and the mechanisms underlying their effects in cancer treatment and suggest using SCFA-producing microbes and SCFAs to increase therapeutic efficacy in several types of cancers.

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권4호
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• pp.261-266
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• 2004

Hyperthermia (HT) in combination with anticancer drugs (ACDs) had proven to more efficacious in various cancers, although efficacies vary according to chemotherapeutic compounds and cancer types. Presently there are few data that compares anticancer efficacies among ACDs under hyperthermic conditions. Therefore, we selected three commonly used ACDs (quercetin, verapamil and doxorubicin) and compared their antitumor effects when each was treated with 43$^{\circ}C$ HT exposure. Firstly, FM3A, a murine breast cancer cell line, was treated with each ACD for 1 h followed by 43$^{\circ}C$ exposure for additional 1 h, and examined the effects of: 1) each drug, 2) 43$^{\circ}C$ HT exposure, and 3) the combination of each drug and 43$^{\circ}C$ HT exposure for 1, 6 and 24 h. The determined overall effects on FM3A cells were arrested cell proliferation, clonogenic efficiency and apoptosis. Pre-treatment of FM3A cells to each ACD followed by 43$^{\circ}C$ HT exposure produced greater antitumor effects including suppressed cell proliferation, reduced clonogenic efficiency and increased apoptotic cell death, compared to ACD treatment or HT exposure alone. Apoptotic cell death occurred in a time-dependent manner. Among the ACDs, antitumor efficacies varied in the order of doxorubicin > verapamil > quercetin. It was concluded that heat exposure during ACD treatment of caner cells may be an important factor to get a better antitumor benefit, even though this benefit may differ from one drug to another.

• 한국동물생명공학회지
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• 제37권1호
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• pp.62-66
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• 2022

To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.