• Title, Summary, Keyword: conventional drugs

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Alternative drug therapies are superior to epidermal growth factor receptor -targeted chemotherapeutic drug responses in non-small cell lung cancer

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.2
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    • pp.10.1-10.8
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    • 2013
  • Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

Cost Analysis of Using a Closed-System Transfer Device (CSTD) for Antineoplastic Drug preparation in a Malaysian Government-Funded Hospital

  • Chan, Huan Keat;Lim, Yik Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.4951-4957
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    • 2016
  • Background: Apart from reducing occupational exposure to cytotoxic hazards, the PhaSeal(R) closed-system transfer device (CSTD) can extend the beyond-use dates (BUDs) of unfinished vials of antineoplastic drugs for up to 168 hours (seven days). In this study, the total material cost incurred by its use in a Malaysian government-funded hospital was calculated. Methods: A list of vial stability following initial needle punctures of 29 commonly-used antineoplastic drugs was compiled. The amount of the materials used, including drugs, infusion bottles, the PhaSeal(R) CSTD and other consumables, was recorded on a daily basis for three months in 2015. The total cost was calculated based on the actual acquisition costs, and was compared with that of a hypothetical scenario, whereby conventional syringe-needle sets were used for the same amounts of preparations. Results: The use of the PhaSeal(R) CSTD incurred a cost of MYR 383,634.52 (USD 92,072.28) in three months, representing an average of MYR 170.5 (USD 40.92) per preparation or an estimated annual cost of MYR 1,534,538.08 (USD 368,289.14). Compared with conventional syringe-needle approach, it is estimated to lead to an additional spending of MYR 148,627.68 (USD 35,670.64) yearly. Conclusion: Although there was a reduction of drug wastage achieved by extending BUDs of unfinished vials using the PhaSeal(R) CSTD, cost saving was not observed, likely attributable to the wide use of lower-priced generic drugs in Malaysia. Future studies should further evaluate the possibility of cost saving, especially in health settings where branded and high-cost antineoplastic drugs are more commonly used.

Metabolism-based Anticancer Drug Design

  • Kwon, Chul-Hoon
    • Archives of Pharmacal Research
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    • v.22 no.6
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    • pp.533-541
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    • 1999
  • Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.

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The Function and Application of Antibiotic Peptides (항생펩타이드의 기능과 적용분야)

  • Lee, Jong-Kook;Gopal, Ramamourthy;Park, Yoonkyung
    • Applied Chemistry for Engineering
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    • v.22 no.2
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    • pp.119-124
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    • 2011
  • Currently, people are exposed to many harmful diseases. Therefore, there are many schemes, such as automation of productive facilities, development of information and communication technology, enhanced the quality of human life and wealth. However, these processes lead to weakened immune system. Thus, people are more vulnerable to infections from pathogens and environmental stress. Misuse and abuse of drugs resulted in the rapid emergence of multidrug-resistant microbes and tumors, therefore, to find new antibiotics are urgently needed. One of them is a peptide-antibiotic, that is not or less occurred a drug-resistance, comparing to conventional drugs. Peptides with various antibiotic activities have been identified from life organisms. The present review provides an overview of activities and application of peptide antibiotics.

Trends and Perspectives in the Development of Antidiabetic Drugs for Type 2 Diabetes Mellitus (제 2형 당뇨병 치료제의 개발 동향)

  • Lee, Soo-Hyun;Lee, Jong-Keun;Kim, Ik-Hwan
    • Microbiology and Biotechnology Letters
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    • v.40 no.3
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    • pp.180-185
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    • 2012
  • Type 2 Diabetes Mellitus, a chronic metabolic disorder which results from a high blood glucose level, is one of the most prevalent and costly diseases of our time. Considering increasing rates of obesity and the aging population in Korea, the number of diabetic patients is likely to rise rapidly in the future. There are five conventional diabetic drugs which work through different mechanisms; sulfonylureas, biguanide, meglitinide, alpha-glucosidase inhibitors, and thiazolidinedione. Although they all have antidiabetic effects, some side effects such as hypoglycemia, weight gain and gastrointestinal intolerance are associated with them. Incretin based therapies, utilizing glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which have a lower risk of adverse side effects, have recently been introduced. At present PPAR-targeting drugs are being actively developed. In this research review, particular emphasis has been placed on the current trends and possible biological targets for the new generation of antidiabetic drugs.

Polymorphism of Clarithromycin

  • Sohn, Young-Taek;Rhee, Jae-Keol;Im, Weon-Bin
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.381-384
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    • 2000
  • It is well recognized that physicochemical properties of drugs are affected by the type of polymorphic crystalline form of drugs. Clarithromycin is known to exist in at least three polymorphic crystalline forms. Since conventional means to obtain the most thermodynamically stable form (Form II) for the antibiotics is known to be associated with a low purity of the stable form, we developed a novel method to improve the purity of the crystalline form by a modification of the preparation process. The new method involved a simple recrystallization of clarithromycin in solvents having 5-12 carbon atoms (e.g., hexane and heptane) or ethers with 4-10 carbon atoms (e.g., isopropyl ether) and, thus, less likely to be associated with the problem in purity of resulting crystal. Differential scanning calorimetry and powder X-ray diffraction were used to compare the crystalline form of the resultant powder with Form IIcrystal prepared by the conventional method. The crystal prepared by the new method was identical to Form IIcrystal of the conventional method as evidenced by the lack of the exothermic peak near 11$0^{\circ}C$ in differential calorimetry scan, indicating that Form IIcrystal could be readily prepared by the new process. Therefore, these data indicated that the improvement in the purity of the Form IIcrystal for clarithromycin as well as a significant cost reduction is likely by the novel method.

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Anticancer Loaded Multi-wall Carbon Nanotube for Targeting Tumors

  • Wang, Wenping;Choi, Jung-Il;Kang, Sang-Soo;Nam, Tae-Hyun;Khang, Dong-Woo
    • Proceedings of the Materials Research Society of Korea Conference
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    • pp.52.2-52.2
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    • 2011
  • Flat form technology for constructing anticancer loaded multi-walled carbon nanotubes (mwCNTs) was introduced in this study. Conventional anticancer drugs, such as MTX (Methotrexate), cisplatin, DOX (Doxorubicin hydrochloride), DAU (Daunorubicin) and EPI (epirubicin) were bio-conjugated with folic acid (FA) for selective targeting tumor cells. Loading efficiencies of the used anticancer drugs on mwCNTs have shown different order of bindings depending on the molecular bind affinity of NH (amine) formation on mwCNTs. MTT assays have shown increased selective target efficiency of FA conjugated mwCNTs on breast cancer cell growth inhibition. All results collectively indicated promising application of mwCNTs as a smart inorganic nanomaterial for selective targeting drug delivery vehicle at tumor tissues.

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Application of MALDI Tissue Imaging of Drugs and Metabolites: A New Frontier for Molecular Histology

  • Shanta, Selina Rahman;Kim, Young-Jun;Kim, Young-Hwan;Kim, Kwang-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.149-154
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    • 2011
  • Matrix assisted laser desorption ionization (MALDI) mass spectrometry is commonly used to analyze biological molecules such as proteins, peptides and lipids from cells or tissue. Recently MALDI Imaging mass spectrometry (IMS) has been widely applied for the identification of different drugs and their metabolites in tissue. This special feature has made MALDI-MS a common choice for investigation of the molecular histology of pathological samples as well as an important alternative to other conventional imaging methods. The basic advantages of MALDI-IMS are its simple technique, rapid acquisition, increased sensitivity and most prominently, its capacity for direct tissue analysis without prior sample preparation. Moreover, with ms/ms analysis, it is possible to acquire structural information of known or unknown analytes directly from tissue sections. In recent years, MALDI-IMS has made enormous advances in the pathological field. Indeed, it is now possible to identify various changes in biological components due to disease states directly on tissue as well as to analyze the effect of treated drugs. In this review, we focus on the advantages of MALDI tissue imaging over traditional methods and highlight some motivating findings that are significant in pathological studies.

Evaluating the Regulation of P-glycoprotein by Phytochemicals Using Caco-2 Cell Permeability Assay System

  • Choi, Ran Joo;Kim, Yeong Shik
    • Natural Product Sciences
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    • v.20 no.1
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    • pp.1-6
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    • 2014
  • P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

Comparative Effectiveness of Biologic DMARDs in Rheumatoid Arthritis Patients with Inadequate Response to conventional DMARDs: Using a Bayesian Network Meta-analysis (Conventional DMARDs 치료에 실패한 류마티스 관절염 환자에서 Biologic DMARDs의 임상적 효과 비교: 베이지안 네트워크 메타분석)

  • Park, Sun-Kyeong;Kim, Hye-Lin;Lee, Min-Young;Kim, Anna;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.25 no.1
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    • pp.9-17
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    • 2015
  • Background: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with insufficient response or intolerance to conventional DMARDs (cDMARDs). These agents have considerable efficacy compared with conventional DMARDs, but only a few head-to-head comparisons among these agents have been performed. The objective of this systematic review and network meta-analysis (NMA) was to compare the relative efficacy of Certolizumab with conventional DMARD to licensed bDMARD with cDMARD therapy for patients who failed to prior cDMARD treatment under the condition of the reimbursement coverage criteria in Korea. Methods: A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 at six months. Bayesian outcomes were calculated as median of treatment effect, probability of the best, Odds Ratio (OR) and probability that OR was greater than one. Results: Compared with other bDMARDs, Certolizumab were associated with higher or comparable ACR response rates; in ACR20, the OR (probability of OR>1) was 2.08 (92.6%) for Adalimumab, 1.86 (85.7%) for Etanercept, 1.89 (79.5%) for Golimumab, 2.36 (92.1%) for Infliximab, 1.79 (87.0%) for Abatacept, 1.74 (80.8%) for Rituximab and 1.82 (86.8%) for Tocilizaumab. In ACR50 and ACR70, the ORs did not present significant differences. Conclusion: Certolizaumab with cDMARD was more effective or comparable than other bDMARDs in patients who failed prior cDMARD treatment.