• 약학회지
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• 제46권2호
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• pp.108-112
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• 2002

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing a resistant subline of HCT15 to adriamycin (CL02), we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW150 was selected for study since an activity against CL02 cells was discovered in the strain. Cytotoxicity-guided fractionation of the culture broth led to the isolation of cystothiazole A and melithiazole F. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Cystothiazole A and melithiazole F demonstrated potent cytotoxicity against certain human cancer cells with $IC_{50}$ values ranging from 0.03~ $0.72{\mu}{\textrm{g}}$/ml. Both compounds were interestingly as active against drug-resistant sublines CL02 and CP70 as against the corresponding parental cells.

• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1271-1284
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• 1997

연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는 바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암 유전자요법의 중요한 대상으로 관심을 모으고 있다. 현재 유전자 이입의 기술적 문제로 생체 외에서 암세포에 유전자 이입을 시행한 후 이를 다시 환자의 생체내로 이식하는 방법이 연구의 주종을 이루고 있다. 그러나 저자들의 과거의 연구를 포함한 여러 연구에서 TNF가 이입된 암세포는 TNF에 대해 내성을 보이는 것으로 증명되었고 이에는 새로이 방어 단백질을 합성하는 것이 관여할 것이라는 시사가 있었다. 이 획득내성의 기전을 밝히는 것이 종양생물학의 이해를 넓히고 보다 효과적인 항암 유전자요법을 개발하기위한 매우 중요한 과제로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.895-901
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• 2013

Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to be involved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptotic resistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2 overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfecting recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed by MTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. Intracellular ROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits. The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with control BIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment. Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2 case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant to ADR-induced apoptosis and ROS might act as an important secondary messenger in this process.

• BMB Reports
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• 제53권2호
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• pp.88-93
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• 2020

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5137-5142
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• 2014

Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

• 종양간호연구
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• 제6권1호
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• pp.66-75
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• 2006

Purpose: The present study was to identify the levels of stress and coping and their relationship in mothers of children with cancer. Methods: A total of 124 mothers were recruited from a university hospital from June 1, to August 31, 2004. Parental Stress Scale developed by Miles and Carter (1983), and the Coping Behavior Patterns developed by McCubbin (1979) were used. Data were analyzed using SAS PC+ 8.0 program. Results: The mean score for the stress level in the mothers of the children with cancer was 195.6 from the range of 0-250. The mean score for the level of coping stress by the mothers of children with cancer was 121.8 from the range of 0-165. The level of coping stress was particularly high when the relationship with their husband was good, and when they felt hope for the children's health status. Conclusions: The most stressful element to the mothers of the children with cancer was the 'treatment and the nursing process for the children.' The frequently used coping methods were 'communication with other parents in the same situation' and 'consultation with the expert.'

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.107-110
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• 2014

Background: Increasing uptake of human papillomavirus (HPV) vaccine should be a priority in developing countries since they suffer 88% of the world's cervical cancer burden. In many countries studies show that age at vaccination is an important determinate of parental acceptability. This study explores parental preferences on age-to-vaccinate for adolescent school-going girls. Materials and Methods: The sample was selected using a two-stage probability proportional to size cluster sampling methodology. Questionnaires were sent home with a random sample of 800 adolescent girls attending 12 schools in Mysore to be completed by parents. Descriptive statistics including frequencies, percentages and proportions were generated for independent variables and bivariate analyses (Chi square test) were used to assess the relationship between independent and appropriate age-to-vaccinate. Results: HPV vaccination acceptability was high at 71%. While 5.3% of parents felt girls should be vaccinated by 10 years or younger; 38.3% said 11-15 years; 14.8% said 16-18 years; 5.8% suggested over 19 years; and 33% didn't know. Only 2.8% of parents would not vaccinate their daughters. Conclusions: Delaying HPV vaccination until later ages may signifivantly increase uptake of the HPV vaccine in India.

• Advances in Traditional Medicine
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• 제2권1호
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• pp.64-67
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• 2002

In the course of screening for new anticancer antibiotics from myxobacteria, strain JW357 was found to produce an antibiotic that was active against several human cancer cell lines. This strain was identified as Angiacaccus disciformis by morphological and cultural characteristics. The antibiotic produced was identified as myxochelin A. It demonstrated significant cytotoxicity against certain human cancer cells with $IC_{50}$ values ranging 1.15 to $2.36{\mu}g/ml$. Myxochelin A was interestingly as active against multidrug-resistant CL02 cells as against the sensitive parental cells (HCT15).

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• BMB Reports
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• 제55권1호
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• pp.39-47
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• 2022

Adoptive cell transfer (ACT), a form of cell-based immunotherapy that eliminates cancer by restoring and strengthening the body's immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident or peripheral blood-modified immune cells into cancer patients to mediate anti-tumor response. Although these immune cells control and eradicate cancer via enhanced cytotoxicity against specific tumor antigens, several side effects have been frequently reported in clinical trials. Recently, exosomes, potential cell-free therapeutics, have emerged as an alternative to cell-based immunotherapies, due to their higher stability under same storage condition, lower risk of GvHD and CRS, and higher resistance to immunosuppressive tumor microenvironment. Exosomes, which are nano-sized lipid vesicles, are secreted by living cells, including immune cells. Exosomes contain proteins, lipids, and nucleic acids, and the functional role of each exosome is determined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cells and NK cells exert anti-tumor effects via proteins such as granzyme B and FasL. In this mini-review, we describe the current understanding of the ACT and immune cell-derived exosomes and discuss the limitations of ACT and the opportunities for immune cell-derived exosomes as immune therapies.