• Title/Summary/Keyword: Drug response

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Outcomes of Second-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in One Institution

  • Lee, Seok Jeong;Kang, Hyun Ju;Kim, Seo Woo;Ryu, Yon Ju;Lee, Jin Hwa;Kim, Yookyung;Chang, Jung Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.1
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    • pp.13-17
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    • 2014
  • Background: This study analyzed the negative prognostic factors in patients who received second-line chemotherapy for advanced inoperable non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the records of 137 patients with inoperable stage III-IV NSCLC who received second-line chemotherapy. The effects of clinical parameters on survival were analyzed and the hazard ratios (HR) for mortality were identified by a Cox regression analysis. Results: Sex, age older than 65 years, smoking history, cell type, T-stage, best response to first-line chemotherapy and first-line chemotherapy regimen were significant negative predictors in univariate analysis. The multivariate analysis showed that patients older than 65 years (HR, 1.530; 95% confidence interval [CI], 1.020-2.297), advanced T stage (T4 vs. T1; HR, 2.273; 95% CI, 1.010-5.114) and non-responders who showed progression with first-line chemotherapy (HR, 1.530; 95% CI, 1.063-2.203) had higher HR for death. Conclusion: The age factor, T stage and responsiveness to first-line chemotherapy were important factors in predicting the outcome of patients with advanced NSCLC who received second-line chemotherapy. The results may help to predict outcomes for these patients in the future.

Testing of the Safety and the Effectiveness of Using Samjeong Pharmacopuncture Solution as Eye drops

  • Seo, Hyung-Sik;Lee, Dong-Jin
    • Journal of Pharmacopuncture
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    • v.15 no.1
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    • pp.23-28
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    • 2012
  • Objective: This experimental study was designed to investigate the safety and the effectiveness of Samjeong pharmacopuncture solution (SPS) manufactured by using a the lowtemperature extract on process. Methods: To identify the safety and the effectiveness of using SPS as eye drops, we performed applied eye irritation tests on rabbits and antibacterial tests for Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium oxysporum, and Candida albicans. The eye irritation test was performed according to the toxicity testing regulation of the Korea Food & Drug Administration (2009. 8. 24, KFDA 2009-116). After SPS had been applied on the left eye of the rabbits, eye irritation in the cornea, iris and conjunctiva was observed on the 1st, 2nd, 3rd, 4th & 7th day. After SPS had been dropped on bacterial species that cause keratitis, the minimum inhibition concentration and the size of the inhibition zone were measured. The anti-bacterial potency was also measured by taking the size of inhibition zone. Results: After SPS had been administered on the left eye of the rabbits, none of nine rabbits were found to show abnormal signs or weight changes. After SPS had been administered on the left eye of the rabbits, no eye irritation in the cornea, iris and conjunctiva was observed on the 1st, 2nd, 3rd, 4th & 7th day. No specific response was detected in MIC for bacterial species Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium oxysporum, and Candida albicans after SPS had been applied. Conclusions: This study suggests that SPS is a non-toxic and non-irritant medicine that does not cause any of eye irritation in rabbits, but it has no antibacterial effects on bacterial species that are well known to cause keratitis. These results suggest that more research is required on extracts from herbal medicines for treating keratitis.

The Experimental study of safety and efficacy in using Soyeom Pharmacopuncture solution as eyedrops (점안용 소염약침액의 안전성 및 유효성 평가)

  • Kang, Eun-Kyo;Seo, Hyung-Sik
    • Journal of Pharmacopuncture
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    • v.12 no.1
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    • pp.21-33
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    • 2009
  • Objective : This experimental study was performed to investigate the safety of Soyeom Pharmacopunture solution manufactured by extraction of alcohol and water. To identify the use of it as eyedrops, the eye irritation test of rabbits and antibacterial test of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium oxysporum, and Candida albicans was performed. Methods : 1. The eye irritation test of this material was performed according to the Regulation of Korea Food & Drug Administration(2005. 10. 21, KFDA 2005-60). After Soyeom pharmacopuncture solution was administered in the left eye of the rabbits, eye irritation of the cornea, iris and conjunctiva was observed at 1, 2, 3, 4 & 7day. 2. After administering Soyeom Pharmacopuncture solution on bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium oxysporum, Candida albicans) which cause Keratitis, MIC(Minimum Inhibition Concentration) and the size of inhibition zone were measured. Anti-bacterial potency was also measured using the size of inhibition zone. Results : 1. After Soyeom pharmacopuncture solution was administered in the left eye of the rabbits, it was found that none of nine rabbits have abnormal signs and weight changes. 2. After Soyeom pharmacopuncture solution was medicated in the left eye of the rabbits, no eye irritation of the cornea, iris and conjunctiva was observed at 1, 2, 3, 4 & 7day. 3. There was no response to MIC on bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium oxysporum, Candida albicans) after Soyeom pharmacopuncture solution was medicated. Conclusions : The present study suggests that Soyeom pharmacopuncture solution is a non-toxic and non-irritant medicine, which does not cause eye irritation in rabbits, but dosen't have anti-bacterial effects on bacterial species which cause Keratitis. These study result recommends that more research on other herbal medicines of eye drop for Keratitis are required.

Effects of baobab extracts on the acute orofacial pain in rat model (흰 쥐의 급성 안면통증모델에서 바오밥 추출물의 효과)

  • Choi, Ja-Hyeong;Kim, Yun-Kyung;Kim, Hee-Jin;Yoon, Hyun-Seo;Hyun, Kyung-Yae;Lee, Min-Kyung
    • Journal of Korean society of Dental Hygiene
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    • v.17 no.5
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    • pp.911-919
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    • 2017
  • Objectives: The baobab tree is a multipurpose, widely-used species with medicinal properties and numerous food uses. The aim of study was to evaluate the effect of oral administration of baobab on the formalin-induced inflammatory pain in rat model injected into the orofacial regions. Methods: Male Sprague-Dawley rats weighing 260-280 g were used. Pain in the orofacial region was induced using two models, 5% formalin was injected $50{\mu}l$ subcutaneously or $30{\mu}l$ in temporomandibular joint (TMJ), respectively. Rats were divided into 4 groups (n=6); formalin, formalin after distilled water (vehicle) or baobab (150, 300 mg/kg). The number of noxious behavioral responses with scratching the facial region was recorded for 9 successive 5-min intervals following formalin injection. Results:There was no significant difference in the first response to the pain between the formalin induced group and the drug administration group. However, in the secondary infusion group, all of the pain medication were responded (Bao 150, 300 mg/kg) (p<0.05). Conclusions:The results showed analgesic effect of baobab on formalin-induced orofacial inflammatory pain. This suggests that the natural product is an effective alternative to the postinflammatory pain control.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

  • Park, Jeong-Kwon;Kim, Sang-Pyo;Song, Dae-Kyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.1
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    • pp.7-12
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    • 2008
  • OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Psychological, Physical and Genetic Traits of Sasang Typology (사상인(四象人)의 생리적 특성 연구)

  • Chae, Han;Hong, Moo-Chang;Bae, Hyun-Su;Shin, Min-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.304-314
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    • 2005
  • The major concept of Sasang typology is that the disease susceptibility and drug response as well as physiological characteristics are presumed to be different depending on their Sasang types. Although characterizing fundamental basis of their traits are crucial in this research field, only pathological susceptibility and physical appearances were thoroughly studied. We evaluated their physiological characteristics by tapping psychological, physical and genetic traits of each Sasang types. After determining the Sasang type of one hundred three college students based on the Questionnaire for the Sasang Constitution Classification, the psychological, physical and genetic traits of each type were analyzed with the Myers-Briggs Type Indicator (MBTI), Bioelectrical Impedance Analysis and genetic polymorphism test, respectively. Each of the Sasang types showed significantly different profiles (Generalized estimation equation, coef=11.88, z=2.13, p=0.033), and could be distinctively classified based on their MBTI scores (discriminant analysis Wilks Lambda=0.611, df=8, chi-square=36.7, p<0.001). Subjects with the So-Eum type (Introversion and Judging) and the So-Yang type (Extroversion and Perceiving) showed contrasting psychological features, however they had similar anthropometric characteristics. Subjects with the Tae-Eum type showed bigger Body Mass Index ($R^2$=0.22, df=4, 74, F=5.07, p=0.001) and body shape compared to others. Although there were no significant differences in G-protein beta-3 subunit polymorphism, angiotensin-converting enzyme polymorphism and Methylenetetrahydrofolate reductase polymprhisms among groups with Sasang types, it was shown that the dopamine system could be one for genetic marker for Sasang typology. These results demonstrated distinctive and essential traits of Sasang typology using reproducible psychometric, anthropometric and genetic evaluations. We also found that the Sasang typology was a bio-psychological typology which could show trait-specific guideline for individualized medicine.

Effects of Pilocarpine and Kainic Acid on EEG and Behavior Activity in Freely Behaving Rats

  • Choi, Byung-Ju;Cho, Jin-Hwa;Lee, Maangee-G.
    • Biomolecules & Therapeutics
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    • v.4 no.2
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    • pp.167-173
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    • 1996
  • This study was undertaken to evaluate a behavior-electroencephalogram (EEG) pattern relationship in pilocarpine- and kainic acid-induced convulsions of rats. Also we intended to examine the effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, and diazepam on the pilocarpine-induced behavioral and electrical seizures in rats. The electrical activities at frontal and hippocampal areas and behavior activities were measured in freely moving rats. At the beginning of the experiments, the rats displayed an exploratory behavior. This awake and moving phase with a low amplitude, irregular, 4-10 Hz wave was followed by a still phase. Pilocarpine (400 mg/kg, i.p.) and kainic acid (0.5 mg/kg, i.c.v.) induced tonic and clonic seizures. The pilocarpine-induced change in electrical activities exhibited a weak correlation with behavioral convulsion at all stages. The amplitude and duration of the electrical response were not linear with the degree of behavioral score. An application of MK-801 (dizocilpine, 7.5 mg/kg) did not affect the amplitudes of the convulsant-induced electrical activities, though the same dose of this drug caused the deformation of the electrical pattern. There was no effect of MK-801 on the behavioral and electrical activities as expected. Diazepam (1 mg/kg) did not affect the amplitude of the electrical activities induced by pilocarpine but changed the pattern of these activities. Our study shows that there is no linear relationship between degree of behavior and amplitude of electrical activities of convulsants. This may indicate that the NMDA receptor stimulation can be processed by the neocortical or hippocampal network in a different way between behavioral and electrical activities.

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Induction of Resistance to BRAF Inhibitor Is Associated with the Inability of Spry2 to Inhibit BRAF-V600E Activity in BRAF Mutant Cells

  • Ahn, Jun-Ho;Han, Byeal-I;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.320-326
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    • 2015
  • The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

Characterization of Tunicamycin as Anti-obesity Agent

  • Song, Ha-Suk;Kim, Hye-Min;Jung, Sook-Yung;Lee, Dong-Hee
    • Biomolecules & Therapeutics
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    • v.17 no.2
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    • pp.162-167
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    • 2009
  • Adipocytes undergo adipocyte stress in the excessive presence of lipid. Adipocyte stress accompanies the typical signs of endoplasmic reticulum (ER) stress: unfolded protein response and overexpression of molecular chaperones. Apoptotic induction in adipocytes is known as a good strategy for treating obesity. The drug "tunicamycin" was tested for its therapeutic potential in inducing apoptosis on differentiating adipocytes of 3T3-L1. When the 3T3-L1 cells, stimulated for adipogenesis, were treated with tunicamycin, they showed typical ER stress symptoms. Despite progression in ER stress, however, the differentiated 3T3-L1 hardly proceeded to apoptosis based on the CHOP protein expression and FACS analysis. This is very different from C2C12, the myogenic counterpart of 3T3-L1, which showed significant apoptosis along with ER stress. This study also characterizes a potential mechanism whereby adipocyte may avoid apoptosis to sustain the pathological state of obesity. The level of GRP94 expression significantly upholds in 3T3-L1 under tunicamycin treatment compared to preadipocytes and C2C-12. When GRP94 expression was inhibited by siRNA, 3T3-L1 showed a higher level of CHOP expression compared to C2C12 cells. In conclusion, adipocytes exert an anti-apoptotic mechanism under ER stress caused by tunicamycin; thus, apoptotic induction in adipocyte is not a viable anti-obesity option. The unusual level of GRP94 may serve as a key role whereby adipocytes reach to the obesity level circumventing the apoptosis.

Current Status of 119 EMT to Violence Experiences (119 구급대원이 경험하는 폭력에 대한 실태조사)

  • Choi, Eun-Sook;Kim, Hee-Jung;Cho, Won-Min;Kang, Dae-Hun
    • The Korean Journal of Emergency Medical Services
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    • v.13 no.3
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    • pp.91-105
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    • 2009
  • Purpose : The purpose of this study was to describe the current status of 119 EMT to violence experiences in Korea. Method : The number of 119 EMT in this study 2522. Self-administering questionnaire data were collected from April 27 to March 8 in 2009. Collected data were analyzed using SPSS 14.0 program. Real number, percentage, mean and standard deviation were calculated. Pearson correlation coefficient was analyzed. Result : 119 EMTs experienced 95.32%-verbal insults, 61.54%-violence aggression, 60.51%- potential violence, 38.70%-physical assault. Within 30 days from the most recent period of violence experienced verbal insults and violence aggression-51.07%, potential violence and physical assault-48.41%. The patients(50.59%) and the patients and patient's carers(38.26%) proved to be violent offender. The main reason of violent act was drug or alcohol addiction(56.15%). Recent exposure to violence was 34.82% by 7 point reward of stress level. 5-point scale showed the average of experiences of violence. Response average of emotional reactions was 2.66 points and that of physical reaction was 2.18 points. Social reaction was 2.06 points. Conclusion : This study was based on the violence experience of 119 EMT. It is necessary to prevent the violence from emergency scene. So we proposed the preventive measure against violence as well as critical incident stress debriefing(CISD). Policy for CISD and stress management will be implemented in the near future in Korea.

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