• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5941-5948
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• 2013

Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.

• Journal of Korean Neurosurgical Society
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• v.63 no.6
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• pp.698-706
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• 2020

Objective : To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. Methods : PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. Results : PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). Conclusion : PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.4
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• pp.167-172
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• 2009

Methotrexate (MTX) in one of the antineoplastic drug and it is known to effective to management of acute lymphoblastic leukemia in children, management of choriocarcinoma and related trophoblastic tumors in women, management of carcinomas of the breast, tongue, pharynx, and tests, maintenance of remission in leukemia and treatment of serve, debilitating psoriasis. Intermediate to high-dose methotrexate administration followed by leucovorin rescue is effective in treatment of carcinoma of the lung and osteogenic sarcoma. Intrathecal administration is effective in treating meningeal leukemia or lymphoma. There are FPIA (Fluorescence polarization immunoassay) and EMIT (Enzyme multiplied immunotechique) methods that measure for MTX. We evaluated the FPIA and EMIT methods. MTX were measured by Hitachi-7600 P-module using EMIT and FPIA using TDX in the sera 60 patients. The performance characteristics evaluated were, light influence, linearity, comparison with FPIA. Also, precision evaluated were three level controls through put following CLSI evaluation protocols (EP10-A). When the MTX value of $4.16{\pm}5.78{\mu}{\mu}mol/L$ (mean, SD) by the Hitachi-7600 P-module was compared with that of $4.05{\pm}5.47{\mu}{\mu}mol/L$ by FPIA, coefficients of correlation of 0.988 was obtained. The regression equation was Y (Hitachi-7600 P-module) = 0.9408 x (FPIA) + 0.1316 (r=0.9885, n=60). CVs of MTX measured by Hitachi 7600 P-module was 6.78% at $0.33{\mu}{\mu}mol/L$, 0.96% at $1.16{\mu}{\mu}mol/L$, and 0.96% at $8.04{\mu}{\mu}mol/L$. The precision was excellent in each group. The linearity was acceptable. We evaluated that MTX is light-sensitive on prolonged exposure to direct sunlight. Comparing with the FPIA using TDX, the Hitachi-7600 P-module using EMIT showed good coefficient of correlation and precision. Therefore the Hitachi-7600 P-module can replace the FPIA for quantitative analysis of MTX.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.465-475
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• 2012

Objectives : This study was performed to investigate the antineoplastic effect of ethanol extracts from Sanguisorbae Radix on cholangiocarcinoma cells that was established from biliary tract cancer tissue. Materials and Methods : Two cholangiocarcinoma cell lines, SNU-1079 and SNU-1196, were studied. The mRNA expression of Caspase 3, 8, 9, Bcl-2, Bax, P53, and P21 was examined by RT-PCR. Cell viability was determined by MTT assay. The cell cycle was analyzed by flow cytometry and apoptosis by cell death detection ELISA kit. Results : Proliferation of SNU-1079 and SNU-1196 was inhibited by Sanguisorbae Radix treatment in a dose-dependent manner. All cells treated with Sanguisorbae Radix showed increased dose- and time-dependent apoptosis. The expression of caspase 3, 8, 9, p53, and p21 was increased in all cells after the treatment of Sanguisorbae Radix. The expression of Bcl-2 was decreased in SNU-1196 and Bax expression was increased in all cells after the treatment of Sanguisorbae Radix. Conclusions : These results suggest that Sanguisorbae Radix would be beneficial in the treatment of cholangiocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.399-402
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• 2012

Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.123-128
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• 2013

Purpose: The aim of study was to investigate the racial or ethnic differences in FDA-approved medications. Methods: Data on racial-based differences of drugs in PDR (Physician's Desk Reference) were analyzed by searching with keywords, "ETHNIC" and "RACE". Results: There were descriptions related to "ETHNIC" in product directions of 53 cases and "RACE" in 266 cases in 2010 PDR. After excluding 30 cases of duplicates, 289 cases were shown of which 28 cases were verified to demonstrate racial or ethnic differences. Drug category showing the higher racial or ethnic differences was cardiovascular drugs (7), followed by alimentary tract and metabolism drugs (6), nervous system drugs (5), and antineoplastic and immunomodulating agents (3). Pharmacokinetic differences between race and ethnicity were observed most frequently; differences in AUC or Cmax showed in 15 drugs and clearance differences in 7 drugs. Conclusions: This study identified the racial differences in medication usage in PDR. Therefore, the results can contribute to safe use of medication in real clinical settings in regards to the racial or ethnic differences.

• Korean Journal of Plant Resources
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• v.6 no.2
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• pp.155-163
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• 1993

21plants, which collected from Korea and Japan, were applied to antitumor and cytotoxic screening tests against sarcoma 180 a ascitec in mice. The results are summariged as follows : 1) The total packed cell volume method has been used for the antimeoplastic screening for from natural higher plants in Korea. By this method, we have found out that Selaginella involves, Patrinia hispida, Archyranthes japonica and Solanum nigrum having significant activity and also Cydonia sinensis and Rubia akane showed slight activity to antitumor 2) The total packed cell volune method has been used for the antineoplastic screening for from natural higher plants in Japan. Among the 21 tested plants, lsodon japonicus having strong antitumor activity and also Torilis japonica, Aralia elata, Leonurus sibiricus and Rubia cordifolia showed significant activity to anticancer tumor while Forsythia spp and Solanum nigrum showed slight activity to antitumor. 3) Among the 21 tested Korea plants, lsodon excisus and Forsythia Koreana showed strong antitumor activity by the V79 cytotoxic cell screening test.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.14-17
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• 2001

Recombinant interleukin-2 (IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with $3{\times}10^6$ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, subcutaneously. Beginning on day 25, experimental groups were treated with a 5-day course of IL-2 (subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that RD-995 tumor grew progressively in control mice. Subcutaneous IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 treated mice were observed compared with the control mice.

• CELLMED
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• v.2 no.3
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• pp.22.1-22.9
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• 2012

The aim of this study is to collate all available data on experiments reporting the antiproliferative, cytotoxic effects of plants and natural products in Morocco in the last two decades. A bibliographic investigation was carried out by analyzing recognized books and peer-reviewed papers, consulting worldwide accepted scientific databases (Scirus, Embase, HighWire, MEDLINE/PubMed, LILACS, Ovid, ScienceDirect, SciELO, Google Scholar). We used medical subject heading terms and the words 'anticancer', 'antiproliferative', 'antineoplastic', 'antitumoral', 'cytotoxic', 'Morocco', to identify relevant articles. Moroccan plants with attributed anti-cancer properties studied as plant extracts that have been evaluated for cytotoxic effects, antitumoral effects, plants with active compounds tested on cancer cell lines, and plants with active compounds that have been assayed on animal models were chosen for this research. In the present study, interest is focused on experimental research conducted on medicinal plants, particularly those which show antiproliferative or cytotoxic activities alongside bioactive components. A total of 20 plant species belonging to 12 families have been identified as active or promising sources of phytochemicals with antiproliferative properties. The plant families, which cover all the species studied in this field, are Lamiaceae (7 species) and Asteraceae (4 species); the most studied species being Argania spinosa (Sapotaceae) and Arisarum vulgare (Araceae), Thymus Genus (Labiateae) and Peganum harmala (Zygophyllaceae). Based on the search results, it is recommended to increase the number of experimental studies and to begin conducting clinical trials with Moroccan plants and their active compounds selected by in vitro and in vivo activities.

• Korean Journal of Pharmacognosy
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• v.17 no.4
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• pp.286-291
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• 1986

Forty herbal drugs which are described to have potential antitumor activity were solvent-fractionated with petroleum ether, ether and ethyl acetate in sequence. The cytotoxic activity was mostly shown in the ether fraction(40.54%) and petroleum ether fraction (35.15%), but scarcely in the water phase (10.8%), meaning that most of the active components had less polar property. Twenty-seven percent of the drugs tested were active, which is higher value than 10.4% of the random sampled drugs The drugs possessing the $ED_{50}$ values less than $10{mu}g/ml$ were the roots of Lithospermum erythrorhizon, Curcuma domestica, Salvia miltiorrhiza, Astragalus membraneceus and Scutellaria indica, the leaves of Panax ginseng, S. indica and Liriodendron tulipifera, the barks of Picrasma ailanthoides and Rhus vernifera, the herbs of Agrimonia pilosa and Siegesbeckia pubescens the seeds of Tricosanthes kirilowii, P. ailanthoides, and the stem of P. ginseng.