• Title/Summary/Keyword: Chemotherapy drugs

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Discovering the Anti-cancer Effects of Ligusticum Chuanxiong through Network-based Pharmacology Analysis and Molecular Docking: An Inquiry into Natural Products (네트워크 기반 약리학 분석 및 분자 도킹을 통한 천궁의 항암 효과 예측: 천연물에 대한 탐구)

  • Do Kyung Han;Jee Won Shon;Eui Suk Sung;Youn Sook Kim;Won G. An
    • Journal of Life Science
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    • v.33 no.11
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    • pp.876-886
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    • 2023
  • In some cases of head and neck cancers (HNC), surgical interventions may result in the loss of organs and/or changes to their functions, thereby significantly affecting the patient's quality of life. As a result, the surgical treatment of HNC patients is often limited to specific cases, and alternative treatment modalities, such as chemotherapy, are considered. However, serious adverse effects caused by chemotherapy, such as severe nausea and vomiting, necessitate the need for the development of adjunctive methods to minimize patient suffering. Chuanxiong, Ligusticum chuanxiong (L. chuanxiong), is a natural herb used in Eastern medicine to treat cerebrovascular disorders and headaches. This study aimed to predict the effect and potential of L. chuanxiong as an auxiliary anticancer drug through network-based pharmacology and molecular docking analysis. The study results showed that 40 out of 41 genes of L. chuanxiong shared common targets of HNC and their proteins could be used to target HNC cells to prevent cancer progression. The results of the functional enrichment analysis confirmed that L. chuanxiong is associated with the neuroactive-ligand metabolism and neurotransmitter pathways, indicating its potential medicinal value as an adjuvant in HNC treatment. Lastly, our findings demonstrated that the active ingredient of L. chuanxiong, (Z)-Ligustilide, has the ATP binding site of heat shock protein 90, a protein known to promote the activation of cancer cells. These results suggest that L. chuanxiong is a promising candidate for developing auxiliary anticancer drugs, and further research could potentially lead to the discovery of newer and safer anti-cancer agents.

Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids

  • Lee, Joong-Won;Kim, Yang-Jee;Choi, Young-Joo;Woo, Hae-Dong;Kim, Gye-Eun;Ha, Tae-Kyung;Lee, Young-Hyun;Chung, Hai-Won
    • Toxicological Research
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    • v.25 no.4
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    • pp.181-188
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    • 2009
  • Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

Multidrug Resistance and Cytotoxicity of Anticancer Drug by Verapamil in Cisplatin Resistant Human Stomach Cancer Cell (Cispatin 내성인 사람 위암 세포주 SNU-1의 복합약제내성 및 Verapamil의 효과)

  • Son, Seong-Kweon;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.9 no.1
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    • pp.75-89
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    • 1992
  • The development of multi drug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell(SNU-1/$Cis_5$) was induced from human stomach cancer cell line(SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/$Cis_5$, We compared the value of $IC_{50}$ - drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNU-1/$Cis_5$ were as follows; vinblastine, > 43.0 ; epirubicin, 22.9 ; dactinomycin, 16.0 ; etoposide, 15.0 ; vincristine, 9.2 ; adriamycin, 5.7 ; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of $10{\mu}M$ verapamil for SNU-1/$Cis_5$ were as follows; vincristine, 13.1 ; epirubicin, 10.0 ; etoposide, 6.3 ; vinblastine, 4.4 ; dactinomycin, 3.6 ; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.

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Assessment of Discoidal Polymeric Nanoconstructs as a Drug Carrier (약물 운반체로서의 폴리머 디스크 나노 입자에 대한 평가)

  • BAE, J.Y.;OH, E.S.;AHN, H.J.;KEY, Jaehong
    • Journal of Biomedical Engineering Research
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    • v.38 no.1
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    • pp.43-48
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    • 2017
  • Chemotherapy, radiation therapy, and surgery are major methods to treat cancer. However, current cancer treatments report severe side effects and high recurrences. Recent studies about engineering nanoparticles as a drug carrier suggest possibilities in terms of specific targeting and spatiotemporal release of drugs. While many nanoparticles demonstrate lower toxicity and better targeting results than free drugs, they still need to improve their performance dramatically in terms of targeting accuracy, immune responses, and non-specific accumulation at organs. One possible way to overcome the challenges is to make precisely controlled nanoparticles with respect to size, shape, surface properties, and mechanical stiffness. Here, we demonstrate $500{\times}200nm$ discoidal polymeric nanoconstructs (DPNs) as a drug delivery carrier. DPNs were prepared by using a top-down fabrication method that we previously reported to control shape as well as size. Moreover, DPNs have multiple payloads, poly lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), lipid-Rhodamine B dye (RhB) and Salinomycin. In this study, we demonstrated a potential of DPNs as a drug carrier to treat cancer.

Apoptotic Response of Human Oral Squamous Carcinoma Cells to Etoposide (Etoposide에 대한 사람구강편평상피암종세포의 세포자멸사 반응)

  • Kim, Gyoo-Cheon;Lee, Kyoung-Duk;Park, Jae-Hyun;Kim, Duk-Han;Park, Jeong-Kil;Park, June-Sang;Park, Bong-Soo
    • Journal of Oral Medicine and Pain
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    • v.30 no.2
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    • pp.231-238
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    • 2005
  • Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.

Cost-Utility Analysis of Pegfilgrastim and Pegteograstim in Patients with Breast Cancer using Doxorubicin and Cyclophosphamide (Doxorubicin과 Cyclophosphamide를 투여받는 유방암 환자에서 Pegfilgrastim과 Pegteograstim의 비용-효용 분석)

  • Kwon, Su Ji;Geum, Min Jung;Kim, Jae Song;Son, Eun Sun;Kwon, Kyeng Hee
    • Journal of Korean Society of Health-System Pharmacists
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    • v.35 no.4
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    • pp.409-417
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    • 2018
  • Background : Febrile neutropenia (FN) is one of the side effects in the patients treated with chemotherapy, and the patients who have FN generally need immediate treatment with extended-spectrum antibiotics and hospitalization. Pegfilgrastim and pegteograstim, which are used for the prevention of FN as a granulocyte-colony stimulating factor (G-CSF), have been granted insurance coverage in the Republic of Korea for certain breast cancer patients using doxorubicin and cyclophosphamide (AC) from September 2016. Methods : The data of the patients with breast cancer using AC regimen and G-CSF were collected retrospectively. This study involves cost-utility analysis of pegfilgrastim and pegteograstim. In this study, we constructed a simple decision tree model for short-term observation and calculated quality-adjusted life year (QALY) and the direct medical costs from the medical provider's perspective. Results : From September 2016 to May 2017, 15 patients were treated with pegfilgrastim and 15 patients were treated with pegteograstim. As a result of dividing the average cost by QALY for each treatment group, it was observed that pegfilgrastim and pegteograstim were consumed 24,923,384 won and 22,808,336 won per 1QALY, respectively. Consequently, incremental cost effectiveness ratio (ICER) showed 2,115,048 won more per pegfilgrastim than pegteograstim per 1QALY, and the cost per 1QALY of both the drugs was lower than 30,500,000 won; the Koreans were willing to pay this amount. Conclusions : This study suggests that pegfilgrastim and pegteograstim can be used to improve the quality of life of breast cancer patients undergoing AC therapy. Among the two drugs, pegteograstim seems to be more cost-effective. However, since this study was conducted as a retrospective observation method on a small scale, it is associated with many limitations. Therefore, a long-term prospective cohort study is needed to supplement the present findings.

A Clinical Effect of Ofloxacin, Prothionamide, Cycloserine Streptomycin(Kanamycin or Tuberactinomycin) in Retreatment of Pulmonary Tuberculosis (폐결핵 재치료에서 Ofloxacin, Prothionamide, Cycloserine, Streptomycin(Kanamycin or Tuberactinomycin) 4제요법의 임상 효과)

  • Song, Ju-Young;Yoo, Min-Kyu;Hong, Jae-Rack;Jeong, Jae-Man;Kim, Young-Jun;Kim, Moon-Shik
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.3
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    • pp.295-301
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    • 1995
  • Background: The serious problems in retreatment of pulmonary tuberculosis are a significant proportion of drug resistance. Preferably retreatment should contain the drugs which has never used before, so drug retreatment is limited in selection. A new antibacterial substance, ofloxacin(OFX) is the activity against mycobacterium tuberculosis and it has been used in the treatment of pulmonary tuberculosis. The present report concerns the result of retreatment of pulmonary tuberculosis patients containing OFX treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow up of 92 smear positive cases, who were treated by four drugs regimen between Mar 1991 and June 1994 at National Kongju Tuberculosis Hospital. Four drugs were, namely prothionamide, cycloserine, ofloxacin and streptomycin(kanamycin or tuberactinomycin). The duration of follow up was over one year. Results: 1) Out of 92 cases with positive sputum AFB smear, 67(73%) achieved the negative conversion. 2) Considering the negative sputum conversion in all the groups, the vast majority(85%) of sputum conversion occurred within the first 4 months. 3) The roentgenological improvement occurred in 49 percent on the whole and when the extent of disease was minimal, moderately, far advanced pulmonary tuberculosis, sputum AFB smear negative response to retreatment was 100%, 93%, 68%, respectively. 4) When the duration of patient's illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 87%, 76%, 65% and 55%, respectively. 5) Adverse reaction to prothionamide, with complaints of gastrointestinal troubles was common and hepatic dysfunction without jaundice was observed in 7 percent, convulsion in 1 percent, that to cycloserine occurred renal dysfunction & psycosis & convulsion, 2%, 1%, 1%, respectively. Tinnitus with KM occurred in 1% and dirrhea with OFX in 4%. Conclusion: The duration of patient's illness was shorter, sputum AFB smear negative response rate was better. Radiologic responses were not remarkable, but extent of disease by national tuberculosis association was smaller, the result of retreatment was better. Adverse reaction of the secondary antituberculosis agent was mainly observed gastrointestinal troubles, as regard to tolerance to the secondary drugs the role of the physician is of very important value and toxic effects can be overcome by the strong confidence.

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Clinical Courses of Cavitary Lesions in Pulmonary Tuberculosis (폐결핵에서 공동성 병소의 임상적 경과)

  • Park, Seung-Kyu;Kweon, Eun-Soo;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.484-492
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    • 2001
  • Background : Pulmonary tuberculosis with a remaining cavitary lesion is considered to be a problem with the course of treatment. In particular, re-treatment cases tend to respond poorly to current anti-tuberculosis agents. Therefore the factors that are related with the poor closure of a cavitary lesion in pulmonary tuberculosis during treatment were evaluated. Methods : A retrospective review of the medical records and chest X -ray films of 68 patients who had chemotherapy for the pulmonary tuberculosis with cavitary lesions was made. All the patients had been followed up for more than 12 months at National Masan Tuberculosis Hospital as of Aug. 2000. Results : The male to female ratio was 3.9:1.72.4% of the patients were between 20 to 50 years of age. 66.2% of the cavitary lesions on the chest X-ray films were confined to the upper lung fields : 36.8% in the right upper lung field and 29.4% in the left upper lung field. 82.4% of the cavities were less than 40 mm in their size, and 83.8% were less than 6 mm thick. The cavitary lesions were closed in 48 cases and remained in 20 cases during a follow-up period of more than 12 months. The factors that are thought to affect to the outcomes of the cavities were age, past medication history, the number of unused drugs, and the number of sensitive drugs. Conclusion : In the treatment courses of pulmonary tuberculosis with cavitary lesions, the following factors are associated with less desirable outcome:an age over 45, a past medication history of more than 2 courses of treatment, The number of unused drugs not exceeding average 6 and the number of sensitive drugs not exceeding average 7.

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The Analysis of Risk Factors of Pulmonary Tuberculosis Patients Failed in Retreatment (재치료실패 폐결핵 환자의 위험인자 분석)

  • Kim, Hyoung-Soo;Lee, Won-Jin;Kong, Seok-Jun;Shon, Mal-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.684-690
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    • 2000
  • Background : The most common cause of treatment failure of pulmonary tuberculosis is early stoppage of treatment or irregular medication. The most important aspect of a retreatment is regular medication provided over a long period. Inadequate treatment may cause drug resistance and prolong the duration of chemotherapy. This study analyzed the risk factors of pulmonary tuberculosis patients, who failed in retreatment, and to use the results as basic data in the management of intractable tuberculosis patients with improving the rate of retreatment success. Methods : We performed a retroactive study of 62 pulmonary tuberculosis patients in retreatment at National Mokpo Tuberculosis Hospital from Jan. 1994 to Dec. 1995. The patients were separated into two groups: group I was retreatment failure and group II was retreatrnent success. For the analysis of risk factors in retreatment failure, we compared the difference between the two groups and tested the confidence limit about results of the results by independent t-test, ${\chi}^2$ test and Fisher's exact test. Results : The treatment failure rate of retreatment patients was 13(21%), and treatment success 49(79%). No significant difference (p>0.05)in age, sex, number of treatment, irregular rate of treatment, extent of the disease & cavitary lesion on the chest X-ray, number of resistance drugs, number of used drugs to medication, number of sensitive bactericidal drugs to medication, rate of sensitive drugs to medication and resisiance to INH & RFP had not significant difference. was found. However, the number of treatment was $2.4{\pm}0.8$ in group I and $1.6{\pm}0.9$ in group II, and had showing a significant difference(p<0.05) between the two groups. Conclusion : The risk factor of retreatment failure was more irregular previous treatment the irregularity of the previous treatment. For reducing the retreatment failure of pulmonary tuberculosis, greater efforts are needed more need to be done to prevent failure of first treatment.

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Three Treatment Methods via the Hepatic Artery for Hepatocellular Carcinoma - A Retrospective Study

  • Ma, Teng-Chuang;Shao, Hai-Bo;Xu, Yang;Xu, Ke
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2491-2494
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    • 2013
  • Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. Results: The overall average change of areas was $240.8{\pm}72.1mm^2$. In the three groups it was $265.0{\pm}58.0mm^2$ vs. $250.5{\pm}51.9mm^2$ vs. $123.7{\pm}26.2mm^2$. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases ($24.0{\pm}13.5$ vs. $20.9{\pm}12.1$ vs. $5.47{\pm}8.20$ and $25.6{\pm}13.5$ vs.$23.2{\pm}12.28$ vs.$5.48{\pm}14.3$) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.