• Title/Summary/Keyword: anticancer drug

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Urinary Mutagenicity, Physical Symptoms and Stress of Nurses Handling Anticancer Drugs (항암제 취급 간호사의 소변중 돌연변이 유발능과 자각증상 및 스트레스)

  • 김봉임
    • Journal of Korean Academy of Nursing
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    • v.26 no.4
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    • pp.963-975
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    • 1996
  • The purpose of this study was to call attention to the mental, physical and occupational hazards of the anticancer-drug-handling nurses by examining the possible urinary mutagenicity and measuring physical symptoms and stress level of the nurses exposed to anticancer drugs. The experimental group of the urinary mutagenicity assay was 14 nurses handling anticancer drugs at the medical wards of a hospital located in J city ; the control group was 12 psychiatric nurses of the same hospital. The test material was the nurses' 24hrs urine, which was concentrated by XAD-2 column chromatography. Tester strains were TA98(±S9 mix), TA100(±S9 mix), TA1535(±S9 mix) and TA1537(±S9 mix) ; Salmonella mammalian-microsomal test(Ames test) was employed for the urinary mutagenicity assay. The physical symptoms of which the nurses experienced were investigated through self-reports on open-questionnaires. The stress levels of the experimental group were measured by a stress measuring instrument developed by this author. Reliability of this instrument was found to be adequate (Cronbach's Alpha=0.9079). To ascertain the urinary mutagenicity of the experimental group, the mean and the standard deviation of the colonies of Tester strains appearing on the minimal plates were taken and compared differences between two groups. T-test was employed for the significance test of two groups. The physical symptoms were compared between the two groups through the analysis of the nurse' self-reports. The mean and standard deviation of the stress levels of the experimental group were also calculated and were examined through t-test. The results were summarized as follows : 1. The experimental group revealed significantly higher urinary mutagenicity both in the activation method test and the non-activation method test of the tester strains TA98, TA100 and TA1535. In the case of TA1537, two groups showed no difference in the non-activation method test, but the activation method revealed difference. 2. The physical symptoms were also much more frequently reported in the experimental group. 79.3% of the experimental group reported more than 1 kind of physical symptoms. On the other hand, 33.2% of the control group complained of 1 kind of physical symptom. The items with high symptom frequency were 'headache', 'itching sensation', 'corneal congestion', 'skin allergy' 3. The mean score of stress in the experimental group was 2.41(range 1-4). The experimental group showed the stress level above 2.0 in the 14 of 15 items in all. The highest stress level were recorded in the following items in the order quoted, 'I fear that anticancer drug may touch any part of body while handling it.', 'I feel concerned there is no protective countermeasure against anticancer drug handling.', 'I am afraid the anticancer drug handling may produce a fetal loss in the future'.

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Characterization of a conjugated polysuccinimide-carboplatin compound

  • Sun Young Lee;Chang Hoon Chae;Miklos Zrinyi;Xiangguo Che;Je Yong Choi;Dong-Hyu Cho
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.31-38
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    • 2023
  • Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

Anticancer Drug Use and Out-Of-Pocket Money Burden in Korean Cancer Patients: A questionnaire Study (국내 암환자의 항암제 사용 및 본인부담비용에 대한 실태조사)

  • Kim, Haesook;Jang, Jinkyung;Sohn, Hyun Soon
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.3
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    • pp.239-250
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    • 2012
  • In recent years, national health insurance(NHI) coverage had been expanded gradually for cancer as a severe disease requiring high level of medical expenditure, to reduce patient's financial burden. But, subjective burdens level for out-of-pocket(OOP) money expense are still considerable owing to high medical cost and decent numbers of services not covered by benefit plan. This study aimed to investigate OOP medical expenditures and identify factors influencing subjective financial burden in cancer patients. A 28-items questionnaire for self-reporting by responders was designed to satisfy study goal and finalized following by one pilot study and experts' verification process. Subjects were enrolled during July to October 2010 through regular meetings organized by five patient or patient-advocacy groups had acknowledged the study purpose. Subjects who aged 20 or more, have histories of cancer diagnosis and anticancer drug use, and voluntarily agreed to participate in this study were recruited. Total 107 subjects included in the analysis have cancer lesions in breast, colon, kidney, liver or stomach at the stages from I to IV. Approximately 73% of them has passed less than 5 years since cancer diagnosis. For the OOP medical expenditure regarding cancer, less 6 million won was in 31%, 6-15 million won in 35% and more than 15 million won in 28% of responders, and more than half responders(58%) felt financial burden subjectively. 63% of responders had subscribed commercial insurances, resulting in money receipts of more than 10 million won since cancer diagnoses in 76% of responders. Logistic regression results showed significant differences in subjective OOP financial burden level depending on gender, household income level, benefit type, commercial insurance money receipt degree, year cancer diagnosed, cancer lesion, therapy type, duration of anticancer drug use, drug listing in national formulary, total OOP medical expenditure and total OOP anticancer drug expense. They had mixed feelings both wishes to expand NHI coverage to reduce financial burden(70%) and no willingness to increase premium(59%). This result suggested that NHI might direct future strategies to reduce absolute total OOP medical cost and expand benefit plan coverage in higher burden groups in particular.

Effects of Anticancer Drug Delivery based on Microbubble and Microbubble-Nanoparticle Complex using Low-Intensity Focused Ultrasound in Breast Cancer Animal Model (유방암 동물모델에서의 저강도 집속초음파를 이용한 마이크로버블 및 마이크로버블-나노물질 복합체 기반 항암제 전달 효율 검증)

  • Baek, Hee Gyu;Ha, Shin-Woo;Huh, Hyungkyu;Jung, Byeongjin;Han, Mun;Moon, Hyungwon;Kim, Sangkyun;Lee, Hak Jong;Park, Juyoung
    • Journal of Biomedical Engineering Research
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    • v.40 no.2
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    • pp.39-47
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    • 2019
  • Ultrasound sonication along with microbubble (MB) could enhance drug delivery to promote the absorption of anticancer drugs into cancers in a noninvasive and targeted manners. In this study, we verify the acute drug delivery enhancement (within an hour) of two representative focused ultrasound driven drug delivery enhancement methods (MB and Doxorubicin-coated Nanoparticle complex (MB-NP) based). Experiments were conducted using in vivo mouse model with MDA-MB-231 breast cancer cell line. Ultrasound generated by single-element 1 MHz focused ultrasound transducer was delivered in pulsed sonication consisted of 0.125 msec bursts at a pulse repetition frequency of 2 Hz for 20 seconds without a significant increase in local temperature (less than $0.1^{\circ}C$) or hemorrhage. Doxorubicin concentrations in tumors were improved by 1.97 times in the case of MB-NP, and 1.98 times by using Doxorubicin and MB separately. These results indicate anticancer drug delivery based on MB and MB-NP can significantly improve the effect of anticancer drugs delivered to tumors in a short time period by using low-intensity focused ultrasound.

Identification of matrix metalloproteinases secreted by human hepatocarcinoma HepG2 cells

  • Lee, Young Jae;Kim, Keun Cheon;Lim, Jeong Mook;Lee, Seung Tae
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.1
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    • pp.62-66
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    • 2022
  • To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.

Alteration of DNA Methylation in Gastric Cancer with Chemotherapy

  • Choi, Su Jin;Jung, Seok Won;Huh, Sora;Chung, Yoon-Seok;Cho, Hyosun;Kang, Hyojeung
    • Journal of Microbiology and Biotechnology
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    • v.27 no.8
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    • pp.1367-1378
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    • 2017
  • Epigenetic alterations such as DNA methylation, histone acetylation, and chromatin remodeling can control gene expression by regulating gene transcription. DNA methylation is one of the frequent epigenetic events that play important roles in cancer development. Cancer cells can gain significant resistance to anticancer drugs and escape programmed cell death through major epigenetic changes, including DNA methylation. To date, several research groups have identified instances of both (i) hypermethylation of tumor suppressor genes, and (ii) global hypomethylation of oncogenes. These changes in DNA methylation status could be used as biomarkers for the diagnosis and prognosis of cancer patients undergoing chemotherapies or other clinical therapies. Herein, we describe genes for which methylation is dependent upon anticancer drug resistance in patients with gastric cancer; we then suggest a significant epigenetic target to focus on for overcoming anticancer drug resistance.

Isolation and Identification of Taxol, an Anticancer Drug from Phyllosticta melochiae Yates, an Endophytic Fungus of Melochia corchorifolia L.

  • Kumaran, Rangarajulu Senthil;Muthumary, Johnpaul;Hur, Byung-Ki
    • Food Science and Biotechnology
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    • v.17 no.6
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    • pp.1246-1253
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    • 2008
  • Phyllosticta melochiae, an endophytic fungus isolated from the healthy leaves of Melochia corchorifolia, was screened for the production of an anticancer drug, taxol on modified liquid medium and potato dextrose broth medium in culture for the first time. The presence of taxol was confirmed by spectroscopic and chromatographic methods of analysis. The amount of taxol produced by this fungus was quantified by high performance liquid chromatography. The maximum amount of fungal taxol production was recorded as $274{\mu}g/L$. The production rate was increased to $5.5{\times}1,000$ fold than that found in the culture broth of earlier reported fungus, Taxomyces andreanae. The fungal taxol extracted also showed a strong cytotoxic activity in the in vitro culture of tested human cancer cells by apoptotic assay. The results designate that the fungal endophyte, P. melochiae is an excellent candidate for an alternate source of taxol supply and can serve as a potential species for genetic engineering to enhance the production of taxol to a higher level.

Development of Anticancer Prodrugs and Tumor Specific Adjuvant Prodrugs for Chemotherapy

  • Moon, Ki-Young
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2000.04a
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    • pp.8-9
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    • 2000
  • Despite the advances made in the past few decades in cancer chemotherapy, many conventional anticancer drugs display relatively poor selectivity for cancer cells. The nonselectivity of anticancer drugs and the development of anticancer drug resistance have been recognized as serious limitations in their clinical usefulness. Therefore, a major challenge in cancer chemotherapy is the development of new anticancer agents with improved selectivity for tumor cells as well as the prevention of the host cell resistance, both of which result in the improvement of therapeutic effect against cancer cells. Cyclophosphamide (CP), a widely used anticancer agent, is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C$_4$- hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) is converted to the ring-opened tautomer to aldophosphamide (Aldo) which subsequently undergoes a base- catalyzed ${\beta}$-elimination to generate cytotoxic phosphoramide mustard (PDA) and acrolein. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA.

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수종(數種) 한약재(韓藥材)의 항암활성(抗癌活性) 연구(硏究)

  • Gang, Tak-Rim
    • Journal of Haehwa Medicine
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    • v.3 no.2
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    • pp.315-321
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    • 1995
  • An extensive anticancer drug screening from natural resources has been carried out primarily using murine tumor model for past fourty years. Recently a new screening program from NCI, so called disease-oriented screening system. has been estabished to detect anticancer drugs that show selective growth inhibition toward variety of tissue specific human solid tumors originated from leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate amd breast. To develope the anticancer drugs from oriental medicinal herbs, we investigated the cytotoxic effects against human tumor cell panels with 23 kinds of MeOH extract of medicinal herbs. Evodiae Fructus, Meliae Toosendan Fructus, Saussureae Radix and Pharbitidis Semen showed strong activities against several tumor cell lines.

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Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

  • Li, Rihua;Xu, Wenting;Eun, Jae-Soon;Lee, Mi-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.41 no.6
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    • pp.381-386
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    • 2011
  • Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.