• Title/Summary/Keyword: Antineoplastic drug

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Platinum Transporters and Drug Resistance

  • Choi, Min-Koo;Kim, Dae-Duk
    • Archives of Pharmacal Research
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    • v.29 no.12
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    • pp.1067-1073
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    • 2006
  • Cisplatin, a platinum coordinated complex, is a widely used antineoplastic agent for the treatment of metastatic tumors of the testis, metastatic ovarian tumors, lung cancer, advanced bladder cancer and many other solid tumors. The cytotoxic action of the drug is often thought to be associated with its ability to bind DNA to form cisplatin-DNA adducts. The development of resistance to cisplatin during treatment is common and constitutes a major obstacle to the cure of sensitive tumors. Although to understand the clinically relevant mechanisms of resistance, many studies have been aimed at clarifying the biochemical/molecular alterations of cisplatin-resistance cells, these studies did not conclusively identify the basis of cellular resistance to cisplatin. In this review, cisplatin resistance was discussed in terms of the relevant transporters, such as copper transporters (CTRs), organic cation transporters (OCTs) and multi-drug resistance related transporters (MDRs). These transporters seem to be contributed to cisplatin resistance through the reduction of drug accumulation in the cell. Better understanding the mechanism of cisplatin resistance associated with transporters will provide the useful informations for overcoming the cisplatin resistance.

Financial Burden of Cancer Drug Treatment in Lebanon

  • Elias, Fadia;Khuri, Fadlo R;Adib, Salim M;Karam, Rita;Harb, Hilda;Awar, May;Zalloua, Pierre;Ammar, Walid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3173-3177
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    • 2016
  • Background: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total case-load. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Materials and Methods: Using utilization and spending data accumulated at MOPH during 2008-2013, the cost to the public budget of cancer drugs was assessed per case and per drug type. Results: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and Non-Hodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Conclusions: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Effect of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelle on Human Glioma Cells

  • Wang, Geng Huan;Shen, He Ping;Huang, Xuan;Jiang, Xiao Hong;Jin, Cheng Sheng;Chu, Zheng Min
    • 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.

Preparation and Evaluation of Paclitaxel Nano-particle Delivery System for Parenteral Formulations (나노입자수송시스템을 이용한 파클리탁셀 정맥주사제의 제조 및 평가)

  • Jeon Il-Soon;Kim Jeong-Soo;Lee Gye-Won;Jee Ung-Kil
    • YAKHAK HOEJI
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    • v.49 no.4
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    • pp.268-274
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    • 2005
  • Paclitaxel is an effective antineoplastic agent against ovarian, colon and breast tumors. But there have been many difficulties to formulate this drug due to the extremely low aqueous solubility. Paclitaxel is currently formulated in a vehicle composed of Cremophor EL and absolute ethanol mixture which is $5\~20$ fold diluted in normal saline or $5\%$ dextrose solution before I.V. injection. However, this formulation has many problems such as allergic reactions and drug precipitation on aqueous dilution. To overcome these problems, we prepared the micelle and microemulsion systems for parenteral administration of paclitaxel by using glycofurol, $Soluto^{(R)}lHS$ 15 and oleic acid. Phase diagram, pH-rate stability, particle size distributions and pharmacokinetics of the systems were studied. Micelles and microemulsions formulated as nano-particle delivery system were physically and chemically stable. Therefore, these formulations might be the promising alternative candidate for the parenteral delivery of paclitaxel.

Preparation and Characterization of BICND-loaded Multi-Layer PLGA Wafer Containing Glycolide Monomer (글리콜라이드 단량체를 함유한 BICNU 함유 다중층 PLGA웨이퍼의 제조 및 특성결정)

  • 채강수;이진수;정제교;조선행;이해방;강길선
    • Polymer(Korea)
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    • v.28 no.4
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    • pp.335-343
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    • 2004
  • Carmustine (l,3-bis(2-chloroethyI)-1-nitrosourea, BICNU) used as antineoplastic drug for the treatment of brain tumor is not appropriate for the long term delivery, because it has short biological half life. Therefore, poly(D,L-lactide-co-glycolide) (PLGA) is useful as drug carrier for the long term delivery due to bulk erosion property. Glycolide monomer is applied to release of BICNU owing to non-toxic and monomeric components after biodegradation of PLGA. In this study, BICNU-loaded PLGA wafers with or without glycolide monomer were fabricated by conventional direct compression method for the sustained release of BICNU. These wafers were observed for their release profiles of BICNU and degradation rates by SEM, NMR, and GPC. Furthermore, we make multi-layer wafers and compare them with release profiles of conventional wafer. From these results, drug release of BICNU-loaded PLGA wafers was increased with increasing the glycolid monomer contents. We confirmed that glycolide monomer and BICNU contents in barrier-layer influenced the drug release profiles and degradation rate.

The Facile and Efficient Synthesis of 8-Chloroadenosine $3^I,5^I$-cyclic monophosphate by phosphorylative cyclization of 8-chloroadenosine and its characterization by$^1 H and 13^C$ NMR spectroscopy

  • Woo, Nam-Tae;Jin, Sun-Yong;Cho, Dae-Jin;Kim, Nam-Sun;Bae, Eun-Hyung;Jung, Jee-Hyung;Ham, Won-Hun;Jung, Young-Hoon
    • Archives of Pharmacal Research
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    • v.20 no.2
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    • pp.176-179
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    • 1997
  • Purine nucleosides were chlorinated by the reaction of acyl chloride in DMF with MCPBA under mild conditions with moderate yields. And, satisfactory method for the synthesis of ribonucleoside-$3^{I},5^{I}$-cyclic phosphates and its characterization by$^{1}H$ and $^{13}C$ nmr spectroscopy is described.

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Trends of clinical trials from 2014 to 2016 in South Korea

  • Huh, Ki Young;Hwang, Jun Gi;Lee, SeungHwan
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.172-176
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    • 2018
  • Mandatory registration of clinical trials in public registry can ensure the transparency of clinical trials. Public clinical trial registry of can provide current chronological and geographical distribution of clinical trial throughout the country. We used public clinical trial registry provided by Ministry of Food and Drug Safety to analyze current status of clinical trial from 2014 to 2016 in South Korea. The number of clinical trials in antineoplastic and immunomodulating agents area was the greatest, followed by cardiovascular system and antiinfectives for systemic use as a whole. From 2014 to 2016, overall number of clinical trials decreased while the number of phase I clinical trials increased. Seoul accounted for more than half number of clinical trials in Korea. Supports for clinical trials in non-metropolitan area needs to be considered.

Quantitative Analysis of Methotrexate using Hitach-7600 P-module (Hitach-7600 P-module을 이용한 Methotrexate 정량분석 평가)

  • Kim, Min-Eui;Cha, Kyong-Ho;Kim, Seung-Hee;Kim, Nam-Joo;Chae, Hyo-Jin
    • 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.

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Analysis of Ethnic Differences in Physician's Desk Reference (Physician's Desk Reference에 나타난 인종차이 분석)

  • Kim, Eun Jung;Lee, Kyung Eun;Gwak, Hye Sun
    • 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.

Effects of Education for Safe Handling of Cytotoxic Drugs on Knowledge and Practice in Oncology Nurses (항암제 안전관리 교육이 간호사의 안전관리 수칙 지식 및 실천에 미치는 효과)

  • Hong, Su-Youn;Cho, Eun-Jung;Yoo, Yang-Sook
    • Asian Oncology Nursing
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    • v.6 no.1
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    • pp.47-53
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    • 2006
  • Purpose: The present study explored the effects of education for safe handling of cytotoxic drugs on knowledge and practice in nurses. Method: Data were collected using a single group with pre and posttest design from 59 nurses at medical and surgical wards in C university hospital from April to June 2005. Questionnaires on the knowledge and practice of the guidelines for safe handling of cytotoxic drugs were asked to complete before and after the education. Result: The education improved nurses' knowledge and practice of the guidelines for safe handling of cytotoxic drugs. The knowledge and practice had a significant positive correlation. Conclusion: These findings show that the education for safe handling of cytotoxic drugs improved the knowledge and practice of nurses. As the knowledge of the guidelines for safe handling of cytotoxic drugs makes a positive association with the practice, it is thought to be required to enhance the education program for nurses.

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