• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.329-336
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• 2000

Backgrounds : The purpose of this study was to identify drugs that can enhance radioresponse of murine fepatocarcinorna. Methods : CSH/HeJ mice bearing 8 mm tumors of murine fepatocarcinorna, HCa-1, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mghg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21$^{WAF1/CIP1}$. Results :Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gemcitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21$^{WAF1/CIP1}$ Conclusion :Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21$^{WAF1/CIP1}$.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.311-319
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• 1996

DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins ($B_1\;and\;B_2$), is a drug currently being developed for hep atic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there's no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.10 no.2
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• pp.244-251
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• 1999

Self-injurious behavior is often showed in mental retardation, especially in autism. Self-injurious behavior has been regarded as a symptom cluster rather than a disease but it is an emergent clinical situation that can directly affect mortality. This case is about a refractory autistic patient who showed a self-injurious behavior of hitting the head repetitively. He was hospitalized and was treated by pharmacotherapy and behavior therapy and for this reason this clinical experience is reported with literature review. The patient is a 7-year old boy who was ward admitted from 1999 April 20 till July 10 into OO hospital OO ward because of self-injurious behavior. During the 12 weeks he had admission treatment. As for the pharmacotherapy, haloperidol was dosed up from 0.5mg to 1.0mg from the 4th week and combination drug therapy was done during the admission with naltrexone 25-50mg. As for the behavioral therapy, Differential Reinforcement of Other behavior was used and regular play therapy was done. To remove the physical restraint, headgear and hard sleeve was used. Currently, OPD follow up treatment is being done and haloperidol 0.5mg and naltrexone 50mg is maintained. The patient’s mother is educated and play therapy is done an hour daily at home. When the patient was released form the hospital, self-injurious behavior was decreased more than the moderate state and remission state is still being maintained at the outpatient clinic.

• Korean Journal of Food Science and Technology
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• v.36 no.2
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• pp.349-354
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• 2004

Predictive growth model of Vibrio parahaemolyticus in modified surimi-based imitation crab broth was investigated. Growth curves of V. parahaemolyticus were obtained by measuring cell concentration in culture broth under different conditions ($Initial\;cell\;level,\;1{\times}10^{2},\;1{\times}10^{3},\;and\;1{\times}10^{4}\;colony\;forming\;unit\;(CFU)/mL$; temperature, 15, 25 37, and $40^{\circ}C$; pH 6, 7, and 8) and applying them to Gompertz model. Microbial growth indicators, maximum specific growth rate (k), lag time (LT), and generation time (GT), were calculated from Gompertz model. Maximum specific growth rate (k) of V. parahaemolyticus increased with increasing temperature, reaching maximum rate at $37^{\circ}C$. LT and GT were also the shortest at $37^{\circ}C$. pH and initial cell number did not influence k, LT, and GT values significantly (p>0.05). Polynomial model, $k=a{\cdot}\exp(-0.5{\cdot}((T-T_{max}/b)^{2}+((pH-pH_{max)/c^{2}))$, and square root model, ${\sqrt{k}\;0.06(T-9.55)[1-\exp(0.07(T-49.98))]$, were developed to express combination effects of temperature and pH under each initial cell number using Gauss-Newton Algorism of Sigma plot 7.0 (SPSS Inc.). Relative coefficients between experimental k and k Predicted by polynomial model were 0.966, 0.979, and 0.965, respectively, at initial cell numbers of $1{\times}10^{2},\;1{\times}10^{3},\;and\;1{\times}10^{4}CFU/mL$, while that between experimental k and k Predicted by square root model was 0.977. Results revealed growth of V. parahaemolyticus was mainly affected by temperature, and square root model showing effect of temperature was more credible than polynomial model for prediction of V. parahaemolyticus growth.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.

• Journal of The Korean Dental Society of Anesthesiology
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• v.3 no.1 s.4
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• pp.19-27
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• 2003

Background: Conscious sedation is a minimally depressed level of consciousness that retains the patient's ability to maintain the airway continuously and to respond appropriately to physical stimulation and verbal command at any time, produced by a pharmacologic or nonpharmacologic method or a combination thereof. In dental anesthesia, a state of sedation in which the conscious patient is rendered free of fear, apprehension, and anxiety through the use of pharmacologic agents. Midazolam is a useful drug of benzodiazepine on minor operation of dentistry. The purpose of this study is to estimate the appropriate dosage protocol of midazolam to the patient receiving intravenous sedation at the department of oral and maxillofacial surgery. Methods: Total subject was fifty-one patients and fifteen patients of this subject were decided to control group (Group I) that they were not received intravenous sedation. The experimental group was randomly subdivided into two groups and each of those groups was administrated to 0.05 mg/kg (Group II) and 0.08 mg/kg (Group III) each other. All patients of the subject were surveyed with postoperative one day questionaire to evaluate the level of sedation. Results: In view of antegrade amnesia, 1. Group II and III were statistically different compared to Group 1, respectively. 2. Group II and III were not statistically different. Conclusions: Apparent antegrade amnesia was found in both groups 0.05 mg/kg and 0.08 mg/kg intravenously administered. So we present the protocol of the department of oval and maxillofacial surgery, Kangnung National University Dental Hospital. But further studies concerning patient's age, body weight, and general condition will be carried out.

• Weed & Turfgrass Science
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• v.5 no.3
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• pp.111-125
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• 2016

Cordgrass (Spartina spp.) is recognized as a highly invasive plant in estuaries throughout the world because of remarkable versatility and resiliency, significant reproduction, strong adaptability, rapid spreading, and vigorous growth. In this review, therefore, to provide insights on the effective management practices, the previous research works were summarized and discussed. Spartina spp. is a perennial halophyte, warm-season (C4) grass that reproduces both sexually through seeds and asexually by rhizomes. Management strategies for cordgrass have included various physical, biological, and chemical controls. Herbicides are usually the most cost-effective means of control. Currently, glyphosate, imazapyr, fluazifop and haloxyfop have been practically used. To improve the control efficacy, a combination of two more than methods (example, mowing-spraying) is needed to be applied consistently every year for at least 3 to 4 years and to be sprayed with enough dry time (>4-6 hr) at an early growth stage (before flowering). Consistently repeated application of same herbicide have to be avoided to prevent an unexpected emergence of herbicide-resistant lines. On the other hand, Spartina spp. have many positive functions for agricultural and eco-engineering purposes. Thus, we have to give more intensive research for effectively managing advantages and disadvantages of Spartina plantations.

• The Korean Journal of Nuclear Medicine
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• v.11 no.1
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• pp.49-58
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• 1977

For the assessment of antithyroid effect of lithium carbonate, it was administered to the 17 hyperthyroid and 5 euthyroid patients, who visited the Seoul National University Hospital from Jan. to Aug., 1977. Thyroid function tests were performed just before the administration of Lithium carbonate, 2 weeks and 2 months after lithium treatment. The results were as follows; 1) In the 5 euthyroid patients, no significant changes in thyroid function tests were obtained before and after lithium treatment. 2) In the 17 hyperthyroid patients, the values of the $T_3RIA$ were $370{\pm}121ng/dl$ 2 weeks after lithium treatment as compared with $506{\pm}121ng/dl$ before the administration, of which the mean percentage fall was 26.9%. $T_3RU$ was varied from $56.8{\pm}8.0%\;to\;47.3{\pm}8.1%$ (16.7% in mean percentage fall), $T_4$ was changed from $24.2{\pm}2.4ug/dl\;to\;22.0{\pm}4.2ug/dl$ (9.1% in mean fall), and $T_7$, from $13.82{\pm}2.25\;to\;10.55{\pm}3.12$ (23.7% in mean fall). 3) In the 5 hyperthyroid patients, serial thyroid function tests were performed 2 weeks and 2 months later. The mean percentage falls of $T_3RIA$ were 36.6 and 61.3%, 2 weeks and 2 months after lithium treatment respectively. Those of $T_3RU$ were 17.5 and 35.1%, those of $T_4$ were 20.4 and 44.0%, $T_7$, 35.0 and 60.7%. 4) Approximately $45{\sim}60%$ of mean fall in thyroid function tests were obtained within the second week. Normal thyroid function tests were observed in 2 among 17 patients within the second week, and 2 among 5 patients within the second month. 18 patients, however, became clinically euthyroid within the 4th week. 5) Single case of hypothyroidism was experienced, and 5 patients (29.4%) complained mild side effects. Lithium salts could be safely administered to hyperthyroid patients who are allergic to thioamides or iodine. Its use is indicated in cases of acute thyrotoxicosis in which it's necessary to reduce hormone levels very rapidly, and lithium-thioamides drug combination is a highly effective and safe means of initial routine control of hyperthyroidism.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.112-112
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• 2019

Baicalein is one of the main flavonoids derived from roots of Scutellaria baicalensis Georgi, a traditional Oriental medicine. Although baicalein has high antitumor effect on several human carcinomas, the mechanism responsible for this property is not unclear. In this study, the data revealed that baicale-ininduced growth inhibition was associated with the induction of apoptosis connecting with cytochrome c release, down-regulation of anti-apoptotic Bcl-xl and increased the percentage of cells with a loss of mitochondria membrane permeabilization. Baicalein also induced the proteolytic activation of caspases and cleavage of PARP; however, blockage of caspases activation by z-VAD-fmk inhibited baicalein-induced apoptosis. In addition, baicalein enhanced the formation of autophagosomes and up-regulated LC3-II/LC3-I ratio. Interestingly, the pretreatment of bafilomycin A1 recovered baicalein-induced cell death suggesting that autophagy by baicalein roles as protective autophagy. Taken together, our results indicated that this flavonoid induces apoptosis and cell protective autophagy. These data means combination treatment with baicalein and autophagy inhibitor might be a promising anticancer drug.