• The Journal of the Korean bone and joint tumor society
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• v.4 no.1
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• pp.13-21
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• 1998

Taxol, the extract from the Taxus brevifolia which is a Pacific yew tree has aroused the interest of the tumor investigators since the 1960s. As well, it is shown to have broad antitumor activity in preclinical experimental models. Its action mechanism is an anti-microtubule effect by duplication of tubulin. The most impressive antitumor activity of taxol has been observed in advanced ovarian cancer and metastatic breast cancer. The purpose of this study was to determine how taxol acts on malignant bone tumor cell lines, to compare its cytotoxic effect with those of other chemotherapeutic agents, and to ascertain the its combination effect with adriamycin. Cell lines used in this study were G-292(osteosarcoma, human), SaOS-2(osteosarcoma, primary, human), and HT-1080(fibrosarcoma, human). Methotrexate, adriamycin, cisplatinum, ifosfamide and taxol were used as testing chemotherapeutic agents and their maximum test concentration were $500{\mu}g/ml$, $200{\mu}g/ml$, $500{\mu}g/ml$, $1000{\mu}g/ml$, and $600{\mu}g/ml$, respectively. The media for cell culture was RPMI-1640 with 10% fetal bovine serum and gentamycin. The results were as follows. The $IC_{50}$ of methotrexate, ifosfamide, cisplatinum, adriamycin and Taxol in G-292 were $2.3{\times}10^{-1}{\mu}g/ml$, $8.0{\times}10^0{\mu}g/ml$, $3.5{\times}10^0{\mu}g/ml$, $9.8{\times}10^{-1}{\mu}g/ml$, $2.7{\times}10^{-2}{\mu}g/ml$ respectively, in SaOS-2 $3.5{\times}10^{-1}{\mu}g/ml$, $1.5{\times}10^1{\mu}g/ml$, $2.8{\times}10^0{\mu}g/ml$, $9.9{\times}10^{-2}{\mu}g/ml$, $1.0{\times}10^{-2}{\mu}g/ml$, respectively, in HT-1080 $4.2{\times}10^{-2}{\mu}g/ml$, $5.4{\times}10^1{\mu}g/ml$, $3.8{\times}10^0{\mu}g/ml$, $5.5{\times}10^{-3}{\mu}g/ml$, $1.1{\times}10^{-3}{\mu}g/ml$, respectively. In conclusion, taxol had very potent cytotoxic effect on the malignant bone tumor cell lines with adriamycin, and was more potent than methotrexate, cisplatinum and ifosfamide. There were synergistic antitumor effects on G-292 and SaOS-2 cell lines in combination test of taxol and adriamycin. From the above results, it would be estimated that taxol could be a new antitumor drug for the malignant bone tumors, providing measures against the side effects and followed by the clinical tests.

• Journal of Life Science
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• v.22 no.4
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• pp.552-558
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• 2012

Severe acute respiratory syndrome (SARS) is a severe respiratory infectious disease caused by a novel human coronavirus, SARS-CoV. The 3CL protease is a key enzyme in the proteolytic processing of replicase polyprotein precursors, pp1a and pp1ab, which mediate all the functions required for viral genomic replication and transcription. Therefore, this enzyme is a target for the development of chemotherapeutic agents against SARS. A large quantity of active SARS-3CL protease is required for development of anti-SARS agents. Here we have constructed overexpression vector for the production of the SARS-3CL protease. The gene encoding SARS-3CL protease was amplified using polymerase chain reaction and cloned into the pET29a expression vector, resulting in pET29a/SARS-3CLP. Recombinant SARS-3CL protease was successfully synthesized by the dialysis mode of the cell-free protein expression system, and purified by three-step fast protein liquid chromatography using HighQ and MonoP column chromatographies and Sephacryl S-300 gel filtration. In addition, the produced SARS-3CL protease was found to be an active mature form. This study provides efficient methods not only for the development of anti-SARS materials from natural sources, but also for the study of basic properties of the SARS-3CL protease.

• Korean Journal of Food Science and Technology
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• v.37 no.3
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• pp.456-464
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• 2005

Antimicrobial drug-resistance is natural response to antimicrobial stress based on selection, which weakens chemotherapy effect. Introduction of large numbers of chemotherapeutic agents to clinical practice has generated strains of microorganisms that survive and multiply in vivo with high-drug concentrations. Methicillin-resistant Staphylococcus aureus (MRSA), bacteria found in normal daily life, can be easily ingested through milk vegetables, and meats, etc. MRSA emerged in many port of the world, increasing complex clinical problems. Therefore, new agents are needed to treat MRSA. Glycyrrhiza uralensis was extracted using 80% MeOH to investigate its antimicrobial activity against MRSA stains KCCM 11812, 40510, and 40512 through bacterial measurement, disc diffusion, and O.D. methods, MIC values, MRSA gene expression investigation, and scanning electron microscope observation. Results revealed MecA, Mecl, MecRI, and FemA were the most highly manifested MRSA genes. Methanolic extract of G. uralensis significantly inhibited MRSA and thus could be used in development of antibacteria.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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• pp.356-366
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• 2012

Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3139-3145
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• 2016

Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organization-enhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 2000-2015. These papers had been cited 54,330 times without self-citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIO-loaded PLGAs and cell-derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR-205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35-year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.287-300
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• 2005

Squamous cell carcinoma (SCC) in head and neck show a variability in the response to chemotherapy, even when it present with similar histological tumor type, grade, and clinical stage. The purpose of present study it to identify predictive bio-marker for the sensitivity or resistance to conventional chemotherapeutic agents, 5-fluorouracil (5-FU) and Cisplatin Oral cancer cell lines were used in present study. MTT assay was performed to evaluate the sensitivity and/or resistance to 5-FU and Cisplatin. And RT-PCR was carried out for evaluation of the mRNA expressions of various genes associated with mutation, inflammation (COX pathway), cell cycle, senescence and extracellular matrix (ECM). The molecules which are correlated with the sensitivity to 5-FU are XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 and HSP47. And the molecules are correlated with the sensitivity to Cisplatin are COX-1, iNOS, eNOS, PCNA, collagen 1 and MMP-9. Taken together, when choosing the appropriate chemotherpeutic agents for patients, considering the molecules which are correlated or reversely correlated is helpful to choose the resonable agents for cancer patients.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• Journal of Gastric Cancer
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• v.4 no.4
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• pp.257-262
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• 2004

Purpose: We reported our preliminary result in 2001. At that time, the follow-up period was too short to evaluate the survival benefit of adjuvant chemotherapy in gastric cancer without serosal invasion. Therefore, we followed those patients for 66 months to determine the long-term effects of adjuvant chemotherapy. Materials and Methods: We analyzed the recurrence pattern, the survival rate, and the disease-specific survival of 135 patients by reviewing their medical records and calling the patients or their relatives. All enrolled patients were included in the intention-to-treat analysis of efficacy. Results: The follow-up rate was $89.6\%$ (121/135), and the median follow-up duration was 66 months. Among the 135 patients, 4 relapsed in group 1 (5-FU+cisplatin), 7 in group 2 (mitomycin C+oral 5-FU), and 6 in group 3 (oral 5-FU only). The overall survival rate was $89\%$ in group 1, $84\%$ in group 2, and $82\%$ in group 3. There were no differences in the overall survival rates and the disease-specific survival rates among the three groups. Conclusion: Oral chemotherapeutic agents have an acceptable effect for adjuvant chemotherapy compared with intravenous agent. However, a large-scale, prospective, randomized study, including a control group, is needed for an exact evaluation.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.95-102
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• 1985

This report offers descriptive data about the drugs utilized in out patient department (OPD) of Yeungnam University Hospital (YUH) in the period of march to august in 1985. The data in this report were produced by the computerized totalization of the number of mentions of individual drugs included in the prescriptions. The 100 drug entries that were most frequently recorded are listed in rank order. The listing is arbiturarily restricted to the drugs that were prescribed as single preparations, the drugs of basis of compound preparations and the drugs of adjuvent or corrective of compound preparations that have significant therapeutic effects either by generic names. And in addition, the listing also involves the compound preparations used in relatively large frequency, and the individual components of which have the unique pharmacological actions each other by proprietary names. And all routes of administrations were allowed. The 10 drugs most frequently named are diazepam, aluminum compounds, acetaminophen, isoniazid, metoclopramide, $polaramine^{(R)}$, carboxymethylcystem, ephedrine, codeine and caroverine in order. The 521,855 drug mentions listed as above are described by the chief therapeutic usage that each is intended to apply generally. The drugs which account the largest proportion of total mentions were those acting on the central nervous system (20.57%), including tranquilhzers and sedative hypnotics (11.71%), analgesic antipyretics (5.55%), antidepressants (2.15%) etc. Gastrointestinal drugs and smooth muscle preparations (18.64%) included antacids and anti-ulcer drugs (9.24%), antiemetics (3.57%), spasmolytics (3.14%) and others. Respiratory drugs (16.11%) included expectorants and cough preparations (10.99%) and bronchodilators (5.12%). Chemotherapeutic agents (15.12%) included the antiTbc drugs (7.09%) most frequently, and the penicillins (3.33%) accounted the largest proportion among the antibiotics. Cardiovascular drugs (5.64%) included cardiac drugs and coronary vasodilator (4.12%) and antihypertensives and vasodilators (1.06%). And anti-inflammatory drugs (4.33%), vitamins of single preparations (3.76%), hormones and their antagonists (3.29%), common cold preparations (3.12%), diuretics (2.81%), drugs supporting liver function (2.02%), drugs affecting autonomic nervous system(1.89%) including anti-glaucomas, atropine and cerebral vasodilators, antihistamine drugs (1.02%) and disinfectants (0.74%) were following in order. The data in this report were compared to those reported by H. Koch, et al. in United States (US), 1981 as "Drugs Most Frequently Used in Office Practice:National Ambulatory Medical Case Survey, 1981." Cardiovascular drugs prescribed in YUH were much less in proportion than in US (10.56%), but gastrointestinal drugs accounted the larger proportion than in US (3.72%). Expectorants and cough preparations in YUH also accounted the larger proportion than in US (2.74%). In conclusion, in the period of march to august, 1985, OPD of YUH prescribed the CNS drugs including diazepam most frequently, and gastrointestinal, repiratory and chemotherapeutic drugs in next orders. It is supposed that the eating habits of Koreans and a unique atmospheric condition in Taegu as a basin were some important factors that affected the proportions of drugs acting on gastrointestinal and respiratory tracts.