• Title/Summary/Keyword: cancer drug

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Effects of Ribosomal Protein L39-L on the Drug Resistance Mechanisms of Lung Cancer A549 Cells

  • Liu, Hong-Sheng;Tan, Wen-Bin;Yang, Ning;Yang, Yuan-Yuan;Cheng, Peng;Liu, Li-Juan;Wang, Wei-Jie;Zhu, Chang-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3093-3097
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    • 2014
  • Background: Cancer is a major threat to the public health whether in developed or in developing countries. As the most common primary malignant tumor, the morbidity and mortality rate of lung cancer continues to rise in recent ten years worldwide. Chemotherapy is one of the main methods in the treatment of lung cancer, but this is hampered by chemotherapy drug resistance, especially MDR. As a component of the 60S large ribosomal subunit, ribosomal protein L39-L gene was reported to be expressed specifically in the human testis and human cancer samples of various tissue origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible A549 cells was isolated, and real time quantitative RT-PCR were used to indicate the transcribe difference between amycin resistant and susceptible strain of A549 cells. Viability assay were used to show the amycin resistance difference in RPL39-L transfected A549 cell line than control vector and null-transfected A549 cell line. Results: The ribosomal protein L39-L transcription level was 8.2 times higher in drug-resistant human lung cancer A549 cell line than in susceptible A549 cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells showed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions and Implications for Practice: The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells.

Genetically Engineered Mouse Models for Drug Development and Preclinical Trials

  • Lee, Ho
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.267-274
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    • 2014
  • Drug development and preclinical trials are challenging processes and more than 80% to 90% of drug candidates fail to gain approval from the United States Food and Drug Administration. Predictive and efficient tools are required to discover high quality targets and increase the probability of success in the process of new drug development. One such solution to the challenges faced in the development of new drugs and combination therapies is the use of low-cost and experimentally manageable in vivo animal models. Since the 1980's, scientists have been able to genetically modify the mouse genome by removing or replacing a specific gene, which has improved the identification and validation of target genes of interest. Now genetically engineered mouse models (GEMMs) are widely used and have proved to be a powerful tool in drug discovery processes. This review particularly covers recent fascinating technologies for drug discovery and preclinical trials, targeted transgenesis and RNAi mouse, including application and combination of inducible system. Improvements in technologies and the development of new GEMMs are expected to guide future applications of these models to drug discovery and preclinical trials.

A Clinical Case Report of Contrast-induced drug eruption patient Treated with Traditional Oriental Medicine (조영제로 유발된 약진(藥疹)환자 치험 1례)

  • Jerng, Ui-Min;Jeong, Jong-Soo;Yoon, Seong-Woo;Park, Jae-Woo
    • Journal of Korean Traditional Oncology
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    • v.12 no.1
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    • pp.75-82
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    • 2007
  • Drug eruption is a cutaneous reaction caused by various drugs. It is a very common drug induced adverse reaction. Contrast media induced drug eruption is rare. But approximately 10% of people injected with contrast media experience adverse reaction, and drug eruption accounts for more than 40% of all adverse reactions. We report a case of mild drug eruption and its treatment process based on korean traditional medicine. The patient is a 50 years old female diagnosed with functional dyspepsia. The patient had gastric discomfort and alternation between diarrhea and constipation. All symptoms showed nearly complete remission with continued korean traditional medical treatment. The patient had been injected with contrast media for Computed tomography(CT) evaluation of her breast cancer history. Rashes appeared on back and abdomen, and urticaria and pruritus appeared on the patient's finger 1 day after injection. We prescribed Goreisan(TSUMURA CO &, TJ-17) and acupuncture on Quchi(LI11), Zusanli(ST36), Yangxi(LI5), Yanggu(SI5). Consequently, the drug eruption showed remarkable improvement. So the author reports korean traditional medicine is effective complementary treatment for drug eruption.

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Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

  • Roy, Madhumita;Mukherjee, Sutapa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1403-1410
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    • 2014
  • Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

Drug Discovery Platform Using Organoids (오가노이드를 활용한 약물 검색 플랫폼)

  • Ju Eun Maeng;Soon-Chan Kim;Myoung-Hyun Song;Nahyun Jeong;Ja-Lok Ku
    • Journal of Digestive Cancer Research
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    • v.10 no.2
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    • pp.82-91
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    • 2022
  • Gastrointestinal cancer accounts for one-third of the overall cancer occurrence worldwide. Pancreatic ductal adenocarcinoma (PDAC) is a type of gastrointestinal cancer that is known to be one of the most fatal among all cancer types, with a 5-year survival rate of less than 8%. Chemotherapy combined with surgical resection is its probable curative option. However, surgery is accessible for only 10-15% of patients diagnosed with PDAC. Organoids show self-organizing capacities and resemble the original tissue in terms of morphology and function. Organoids can also be cultured with high effectiveness from tumor tissues derived from each patient, making them an extremely fitting model for translational uses and improving personalized cancer medicine. Enhancing drug screening platforms is necessary to apply personalized medicinebased organoids in clinical settings.

Cytotoxic Components in an Extract from the Leaves and Stems of Stauntonia hexaphylla

  • Zhao, Jing;Yim, Soon-Ho;Um, Jung-In;Park, Si-Hwan;Oh, Eun-Sang;Jung, Da-Woon;Williams, Darren R.;Lee, Ik-Soo
    • Natural Product Sciences
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    • v.20 no.2
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    • pp.130-134
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    • 2014
  • An investigation was carried out to identify novel anti-cancer compounds from Korean indigenous plant extracts. Bioassay-guided fractionation and chemical investigation of the EtOAc extract from the leaves and stems of Stauntonia hexaphylla resulted in the isolation of two active compounds, hederagenin 3-O-${\alpha}$-L-arabinoside (1) and quercetin (2). The structures of these compounds were elucidated by spectroscopic methods, including UV, IR, MS, NMR techniques and compared with previous spectroscopic data. The cytotoxic effects of fractions and compounds on HCT116 human colon cancer cells were evaluated using the MTT assay. Quercetin showed a stronger anti-cancer effect when compared to hederagenin 3-O-${\alpha}$-L-arabinoside.

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.

Enhanced Anti-tumor Efficacy of Aspirin Combined with Triptolide in Cervical Cancer Cells

  • Chen, Rong-Hui;Tian, Yong-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3041-3044
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    • 2013
  • Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

Effects of Naetakcheonkeumsan and It’s Gamypang on the Lymphocytes and Cancer cells (內托千金散 및 그 加味方이 마우스의 免疫細胞 및 癌細胞에 미치는 效果)

  • Yang, Gi-ho;Jeong, Hyun-woo;Choi, Jung-hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.13 no.1
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    • pp.44-59
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    • 2000
  • Naetakcheonkeumsan(NCS) was a drug that treated carbuncle and cellulitis. So, the purpose of this Study was to investigate effect of NCS on the anti-cancer and proliferation of lymphocytes in normal mouse group, L1210 cells-transplanted mouse group and anti-cancer drug (vincristine) 0.005mg/kg were injected mouse(Ll210 cells-transplanted) group. We used NCS extract with freeze-dried, 8wks-old male mice, and Ll210 cell lines for this Study, The proliferation of cells was tested using a colorimetric tetrazoliun assay(MTT assay). The results of this Study were obtained as follow ; Group C(NCS plus Rehmanniae Radix Preparat administered group) inhibited proliferaion of lymphocytes in normal mouse group and Ll210 cells transplanted mouse group. Group A(NCS administered group) and Group B(NCS plus Cervi pantotrichum Cornu administered group) inhibited proliferation of Ll210 cells in Ll210 cells-transplanted mouse group and anti-cancer drug were injected mouse(Ll210 cells-transplanted) group. Group C incresed proliferation of L1210 cells in L1210 cells-transplanted mouse group, but inhibited in anti-cancer drug(vincristine) 0.005mg/kg were injected mouse(L1210 cells-transplanted) group.

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P-Glycoprotein-Based Drug-Drug Interactions: Preclinical Methods and Relevance to Clinical Observations

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.127-135
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    • 2004
  • Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.