• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.127-131
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• 2013

Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.63-73
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• 2012

Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.188-198
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• 2013

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5037-5041
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• 2015

Background: An hCG regression curve has been used to predict the natural history and response to chemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestational trophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/CO resistance in GTN. Materials and Methods: Eighty-one women with GTN treated with EMA/CO were classified as primary high-risk GTN (n = 65) and single agent-resistance GTN (n = 16). The hCG levels prior to each course of chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves. Diagnostic performance was evaluated for an optimal cut-off value. Results: The median hCG levels were 264,482 mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN, respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course of chemotherapy, respectively. The hCG level of ${\geq}118.6mIU/mL$ mIU/mL at the 5thcourse of EMA/CO predicted the EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%. Conclusion: EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curve in combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy.

• Journal of Korean Neurosurgical Society
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• v.41 no.6
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• pp.397-402
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• 2007

Objective : Balloon cells and dysplastic neurons are histopathological hallmarks of the cortical tubers of tuberous sclerosis complex [TSC] and focal cortical dysplasia [FCD] of the Taylor type. They are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. P-glycoprotein [P-gp] is the product of multidrug resistance gene [MDR1], and it maintains intracellular drug concentration at a relatively low level. The authors investigated expression of P-gp in balloon cells and dysplastic neurons of cortical tubers in patients with TSC. Methods : An immunohistochemical study using the primary antibody for P-gp, as an indicative of drug resistance, was performed in the cortical tuber tissues in two patients of surgical resection for epilepsy and six autopsy cases. Results : Balloon cells of each lesion showed different intensity and number in P-gp immunopositivity. P-gp immunopositivity in balloon cells were 28.2%, and dysplastic neurons were 22.7%. These immunoreactivities were more prominent in balloon cells distributed in the subpial region than deeper region of the cortical tubers. Capillary endothelial cells within the cortical tubers also showed P-gp immunopositivity. Conclusion : In this study, the drug resistance protein P-glycoprotein in balloon cells and dysplastic neurons might explain medically refractory epilepsy in TSC.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.412-420
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• 2000

Background : There is increasing concern in many countries about the problem of drug-resistant tuberculosis. Prevalence of primary drug-resistant tuberculosis is the optimal epidemiological indicator for long term monitoring of national tuberculosis control program. Our purpose was The purpose of our study is to assess clinical characteristics and socioeconomic status of patients with drug-resistant tuberculosis. Method : We studied 68 cases with drug-resistant Mycobacterium tuberculosis infection diagnosed at the Ewha Womans University Mokdong Hospital from March, 1995 to February, 2000. Results : Patients with primary drug-resistant tuberculosis(PDR) were younger (39.6$\pm$16.3 years vs. 48.2$\pm$16.5 years ; p<0.05), had more population of less than more were under the age of 40 years aged -group(62.9% vs. 36.4% ; p<0.05) and were more highly educated than those with acquired drug-resistant tuberculosis(ADR)(38.9% vs. 11.1% ; p<0.05). In patients with ADR, the rates of familial history of tuberculosis and living in a rented house residence in a rented house were increased higher than compared with to those of patients with PDR. Patients with ADR had more involved lobes(2.0$\pm$0.8 vs. 1.4$\pm$0.7 ; p<0.01) and longer treatment duration than those with PDR(18.3$\pm$7.2 months vs. 10.6$\pm$6.3 months ; p<0.05). Patients with ADR showed larger numbers of resistant were resistant to more number of drugs, lower hospitalization rate and higher rate of self-interruption of medication than those with PDR. In patients with PDR, mono-drug resistance was increased, whereas poly- and multi-drug resistances were decreased compared with those with ADR. Resistance to isoniazid was the highest among antituberculosis drugs, and resistance to isoniazid in patients with ADR was higher than that in patients with PDR(90.9% vs. 71.4% ; p<0.05). Conclusions : Patients with ADR were more likely to include more population be of lower socioeconomic class, and patients with PDR seem seemed to be young and socially active population. For control of drug-resistant Mycobacterium tuberculosis infection, proper isolation and prevention of patient with drug-resistant tuberculosis are needed.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.89.1-89.8
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• 2018

Objective: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%-30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. Methods: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. Results: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p<0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. Conclusions: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%-30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.2
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• pp.64-71
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• 2018

Objectives The purpose of this study is to examine the correlation of antibiotics administration duration and antimicrobial resistance by reviewing domestic and foreign literatures. Methods We searched literatures dated up to 23 February, 2018 in PubMed and Cochrane Library using terms of "Anti-Bacterial Agents", "Carrier State", "Nasopharynx", "Drug Administration Schedule", and also searched via RISS (Research Information Service System), KISS (Koreanstudies Information Service System), DBpia (DataBase Periodical Information Academic) using terms of antibiotics, resistance, and dose. Results In comparison with shortened and standard antibiotic course, longer treatment duration is associated with greater antimicrobial resistance or non-significant difference, but we cannot find literature that shortened antibiotic course increases antimicrobial resistance on human nasopharyngeal flora. Conclusions Currently, there is no evidence that completing the standard antibiotic course reduces antimicrobial resistance. It can be a strategy for reducing antibiotic use to apply Korean medicine treatment, as well as short-course antibiotic therapy or delayed antibiotic prescription. Additional well-designed trials should be conducted in domestic and foreign settings about the appropriate duration of antibiotic therapy.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.05a
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• pp.1-4
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• 1998

Impaired insulin action in Type 2 diabetes is thought to lead to hyperglycemia, with both environmental and complex genetic factors playing key roles. Although the primary lesion in Type 2 diabetes is unknown, a number of studies suggest that metabolic defects in the liver, skeletal muscle and fat, and pancreatic ${\beta}$-cells contribute to the disease. These metabolic abnormalities are characterized by the overproduction of hepatic glucose, impaired insulin secretion, and peripheral insulin resistance. In current pharmacological treatment of Type 2 diabetes, sulfonylurea (SU) drugs have mainly been used as oral hypoglycemic drugs to stimulate endogenous insulin secretion from ${\beta}$ cells. SU drugs, however, sometimes aggravate the disease by causing fatigue of the pancreatic ${\beta}$ cells, which leads to reduced drug efficacy after long-term treatment. This class of drugs also leads to enhanced obesity arising from the stimulation of endogenous insulin secretion in obese Type 2 diabetic patients, plus an increased incidence of SU-induced hypoglycemia. Since 1980, a major challenge has been made by us to develop a potential pharmacological therapy for the treatment of insulin resistance in peripheral tissues and/or suppression of abnormal hepatic glucose production in Type 2 diabetic patients. Such a drug would be expected to have fewer side effects and retain long-term efficacy.

• Parasites, Hosts and Diseases
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• v.50 no.4
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• pp.379-384
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• 2012

Resistance of Plasmodium spp. to anti-malarial drugs is the primary obstacle in the fight against malaria, and molecular markers for the drug resistance have been applied as an adjunct in the surveillance of the resistance. In this study, we investigated the prevalence of mutations in pvmdr1, pvcrt-o, pvdhfr, and pvdhps genes in temperate-zone P. vivax parasites from central China. A total of 26 isolates were selected, including 8 which were previously shown to have a lower susceptibility to chloroquine in vitro. For pvmdr1, pvcrt-o, and pvdhps genes, no resistance-conferring mutations were discovered. However, a highly prevalent (69.2%), single-point mutation (S117N) was found in pvdhfr gene. In addition, tandem repeat polymorphisms existed in pvdhfr and pvdhps genes, which warranted further studies in relation to the parasite resistance to antifolate drugs. The study further suggests that P. vivax populations in central China may still be relatively susceptible to chloroquine and sulfadoxine-pyrimethamine.