• Bulletin of the Korean Chemical Society
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• v.34 no.7
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• pp.1972-1984
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• 2013

Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.

• Biomolecules & Therapeutics
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• v.3 no.2
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• pp.122-131
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• 1995

Five human cancer cell lines (HeLa S3, Hep 3B, KATO III, Hs 683, HeLa MR) and one human normal cell line (WI-38) were examined cell viability, northern blot analysis, western blot analysis, and in situ hybridization for the expression $O_{6}$ -methylguanine-DNAmethyltransferase (MGMT), which can repair $O_{6}$ -methylguanine produced in DNA by alkylating agents. In cell viability test, the lethal sensitivities of each strain against anti-tumor drug N,N-bis(2-chloroethyl)- N-nitrosourea (BCNU) were counted, and both BCNU treated and untreated cell extracts were examined for their MGMT inducibility by RNA dot blot analysis. Cell lines did not show MGMT induction by BCNU pretreatment. Tlle MGMT activity was assayed by measuring the $^3$H radioactivity transferred from the substrate DNA containing [methyl-$^3$H)-O$_{6}$ -methylguanine to acceptor molecules in the cell extracts. Extracts from the majority of tumor strains and normal cells contained substantial MGMT activity of varying degree, while the known Mer$^{[-10]}$ cell (lacked or severely depleted in MGMT activity) Hela MR, and Hs 683 (proved to be Mer$^{[-10]}$ ) were much more sensitive to BCNU than the rest of tumor strains, as measured by cell viability test. Overall results above, KATO III showed the highest expression level of MGMT among the strains examined. Furthermore, with all the tumor and normal strains tested, a good correlation was observed between MGMT expression and cellular resistance to BCNU. The varying levels of expression of MGMT in human cancer cells found in this study should provide a molecular basis for MGMT expression among tumor strains from different tissue origin, the information of antitumor agents selection for chemotherapy of cancers.

• Toxicological Research
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• v.24 no.2
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• pp.101-107
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• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3057-3062
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• 2013

Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.44.1-44.11
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• 2023

Background: A series of breast cancer cases were recently reported in a tertiary university hospital in South Korea. Nurses are generally exposed to risk factors for breast cancer such as night shift work, antineoplastic agents, and job strain. However, the epidemiological evidence of excess incidence among nurses remains lacking. This study aims to investigate the excess incidence of breast cancer among nurses in a tertiary university hospital and provide epidemiological evidence of occupational risk factors. Methods: A retrospective cohort was developed using personnel records of female workers in the nursing department who worked from January 2011 to June 2021 in a tertiary university hospital in South Korea. Sick leave records were used to identify cases of breast cancer. The standardized incidence ratio of breast cancer among nurses was compared to the general population. Results: A total of 5,509 nurses were followed up for 30,404 person-years, and 26 breast cancer cases were identified. This study revealed a significantly increased breast cancer incidence among all included nurses, with a standardized incidence ratio of 1.65 (95% confidence interval [CI]: 1.08-2.41), compared to the general population. Workers, who handle antineoplastic agents in their representative department and current and/or former department, had significantly elevated breast cancer standardized incidence ratios of 2.73 (95% CI: 1.008-5.94) and 3.39 (95% CI: 1.46-6.68), respectively. Conclusions: This study provides significant evidence of increased breast cancer risk among nursing staff in a hospital setting, particularly those who handle antineoplastic drugs. Measures that reduce exposure to risk factors should be implemented, especially anticancer drugs, to protect healthcare professionals. Further research at a national level that focuses on healthcare workers is necessary to validate breast cancer incidence and its contributing factors.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1655-1658
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• 2008

Cyanobacteria, blue-green algae, are a rich source of bioactive secondary metabolites with many potential applications. The ubiquitin-proteasome proteolytic system plays an important role in selective protein degradation and regulates cellular events including apoptosis. Cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Thus, proteasome inhibitors can be potential anticancer agents. Cyanobacteria have been shown to be a rich source of highly effective inhibitors of proteases. A proteasome inhibitor was screened from an extract of the culture of Scytonema hofmanni on the basis of its inhibitory activity, which led to the isolation of nostodione A with an $IC_{50}$ value of 50${\mu}M$. Its structure was determined by spectroscopic methods such as $^{1}H$-NMR and ESI-MS spectral analyses.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1359-1363
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• 2006

Novel anthracycline analogues 2-9 as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium lactate, and stearic acid, respectively. Compounds 3-5 and 7-9 were prepared by the reaction of either daunomycin (1a) or doxorubicin (1b) with L-lactic and stearic acids in the presence of EDCI/PP reagents.

• International Journal of Internet, Broadcasting and Communication
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• v.12 no.3
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• pp.139-148
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• 2020

Red rose petals are usually disposed but they are an abundant source of phenolics and traditionally used as food supplement and as herbal medicine. Of the Various phenolics, they are known to have anticancer, antioxidant, and anti-inflammatory properties. In this study, we investigated the anti-inflammatory effects of red rose ethanolic extracts (GRP) on lipopolysaccharide (LPS)-activated RAW 264.7 cells. The results demonstrated that pretreatment of GRP (500㎍/mL) significantly reduced NO production by suppressing iNOS protein expression in LPS-stimulated cells. Anti-inflammatory effects by red rose petals were observed in the following. Red rose petals inhibited the translocation of NF-κB from the cytosol to the nucleus via the suppression of IκB-α phosphorylation and also inhibited LPS-stimulated NF-κB transcriptional activity. These findings suggest that red rose petals exert anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of red rose petals. Therefore, red rose petals could be regarded as a potential source of natural anti-inflammatory agents.

• KSBB Journal
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• v.15 no.3
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• pp.293-298
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• 2000

${\beta}$-Glucan a kind of polysaccharide which is particularly abundant in Agaricus blazei is known as the bioactive materials especially anticancer agents. The process development of the isolation and the purification process of water soluble ${\beta}$-glucans from A. blazei was achieved. and the process operation variables were optimized. Crude polysaccharides (CR.PS) were obtained from A. blazei by hot water extraction filtration solvent precipitation dialysis and freeze drying. Neutral and acidic fraction of polysaccharides were separated from crude polysaccharides by ion chromatography and then high molecular weight and low molecular weight fraction were separated from neutral fraction by gel chromatography. Quantitative and qualitative analysis of each compounds were performed with FT-IR NMR spectroscopy. Based on these analysis the optimal conditions of temperatures operating time organic solvent volume for precipitation and dialysis time were determined.

• Korean Journal of Pharmacognosy
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• v.38 no.4
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• pp.334-338
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• 2007

Roots of Rumex crispus (Rc) (Polygonaceae) has been used as therapeutic agents of acute and chronic cutaneous diseases, cathartics, fever and jaundice in folk medicines. Recently, Seeds of Rc has known as a digestive, an anticancer agent and a remedy of acute hepatitis, among many traditional folk medicines. So far it isn't reported about pharmacological effects of Rumecis Semen. The present study describes the preliminary evaluations of biological activities, anti-inflammatory activity (AA, Carrageenan) analgesic activity (writhing test), and hepatoprotective activities ($CCl_4$), of its methanol extract, ethyl acetate fraction and butanol fraction. Among them butanol fraction showed the highest activity in analgesic acivity.