• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.1
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• pp.28-35
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• 2008

Purpose: The aim of this study is to report the efficacy of infliximab, a monoclonal antibody directed against tumor necrosis factor alpha which is used for both treatment of refractory pediatric Crohn disease (CD) and induction of remission. Methods: Among pediatric patients who were diagnosed with CD at Samsung Medical Center between March 2001 and August 2007, a total of 16 patients were given infliximab to treat conventional therapyresistant refractory CD and severe active CD for induction of remission. Patients needing maintenance therapy were treated with an infliximab infusion every 8 weeks, and fistulizing CD patients occasionally received the infusion upon the condition that a fistula developed. The efficacy of treatment was assessed by comparing the Pediatric Crohn Disease Activity Index (PCDAI), Hct, ESR, CRP, and serum albumin levels using paired t-test. Results: The male/female ratio was 13:3, and the median age was 13 years (range, 21 months~15 years). The patients included 7 cases of therapy-resistant refractory CD, 7 cases of severe active CD, and 2 cases of fistulizing CD. Mean PCDAI before infliximab therapy was 34.19${\pm}$14.96, and mean follow-up PCDAI within 2 to 4 weeks after the last infusion was significantly lower, at 6.88${\pm}$10.31 (p=0.000). Hematological markers such as ESR (p=0.000), serum albumin (p=0.016), and CRP (p=0.009) also improved significantly after infusion. Remission was achieved in 2 of 4 patients refractory to conventional therapy. Among 3 steroid-dependent patients, 2 were able to discontinue steroid therapy, and dose reduction was possible in 1 patient. Remission after top-down therapy without prior use of other immunomodulators was achieved in 6 weeks in all 7 of the patients who had severe CD. Nine of ten refractory fistulizing CD patients also showed improvement after infliximab therapy. Conclusion: Infliximab was effective in pediatric refractory CD for induction of remission and maintenance therapy, as well as in severe CD for top-down induction therapy. Furthermore, infliximab has contributed to steroid cessation and dose reduction. Long-term follow-up evaluation is needed to determine safety and efficacy of infliximab in the future.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.19-26
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• 1997

Purpose : This study is to report experience with Fractionated Stereotactic Radiation Therapy (FSRT) for locally recurrent nasopharynx cancer after curative conventional radiation therapy. Materials and Methods : Three Patients with locally recurrent and symptomatic nasopharynx cancer were given FSRT as reirradiation method between the Period of September of 1995 and August of 1996 For two Patients, application of FSRT is their third radiation therapy directed to the nasopharynx. Two patients were given low dose chemotherapy as radiation sensitizer concurrently with FSRT Authors used 3-dimensional coordinate system by individually made, relocatable Gill-Thomas-Cosman (GTC) stereotactic frame and multiple non-coplanar arc therapy dose Planning was done using Xknife-3. Total of 45 Gy/18 fractions or 50 Gy/20 fractions were given. Results : Authors observed satisfactory symptomatic improvement and remarkable objective tumor size decrease by follow-up MR images taken 1 month Post-FSRT in ali three patients, while no neurologic side effect attributable to reirradiation was noticed. Two died at 7 and 9 months with loco-regional and distant seeding outside FSRT field, while one patient is living for 4 month. Conclusion Authors experienced satisfactory therapeutic effectiveness and safety of FSRT as reirradiatlon method for locally recurrent nasopharynx cancer Development of more effective systemic chemotherapeutic regimen is desired for distant metastasis

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.5
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• pp.272-281
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• 2003

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.

• Journal of Life Science
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• v.20 no.9
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• pp.1324-1331
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• 2010

Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

• Korean Journal of Head & Neck Oncology
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• v.23 no.2
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• pp.153-156
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• 2007

Objectives : We study the feasibility and pharmacokinetics of cisplatin concurrent chemoradiation for advanced head and neck cancer patient undergoing hemodialysis. Materials and Methods : A 57-year old male with end stage renal disease developed stage III external auditory canal cancer. Complete resection surgery was done. Postoperative 6 months, local recurrence was occurred. Despite excision and adjuvant radiotherapy, local tumor was recurred. We decided to treat a cisplatin concurrent chemoradiotherapy. Cisplatin was administered at a dose of $20mg/m^2$ for 30 min. Hemodialysis was started 30 min after completion of the cisplatin infusion and performed for 4 hours. Hemodialysis was performed on day 3 and 5 of chemotherapy. Plasma samples were collected at specified times after administration of cisplatin. Result : At the end of the third cycle of cisplatin concurrent chemoradiotherapy, the tumor size was markedly decreased. The maximum plasma concentrations of plasma platinum and free platinum were 0.74 and $0.37{\mu}g/ml$ respectively. The area under the curve of plasma platinum and free platinum were 94.7 and $11.3{\mu}g{\cdot}h/ml$ respectively. Conclusion : We report a case of Cisplatin concurrent chemoradiation for hemodialysis patient with advanced head and neck cancer and suggest full dose cisplatin concurrent chemoradiotherpay is tolerable for these patients.

• The korean journal of orthodontics
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• v.26 no.1 s.54
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• pp.83-94
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• 1996

Substance P is one of the neuropeptide which presents highly in tension site of periodontal ligament during the orthodontic tooth movement. It has bnn also hon as one of the neuropeptides which cause neurogenic inflammation in various tissues and organs. However, there is no report about the effect of substance P on major extracellular matrix protein, collagen production. The purpose of this study was to evaluate the collagen production by substance P in human periodontal ligament cell. The collagenase-digestion method was used to evaluate collagen production and also used Northern blot hybridization for the evaluation of collagen mRNA level. This study also Included in terms of prostanglandins and gelatinase production with respect to collagen production. For the collagen degradation, zymography was used to estimate denatured collagen degradation. Dose-dependent effect of substance P on noncollagen protein, collagen, and percent collagen was that substance P increased noncollagen protein synthesis, but decreased collagen sytnsis. So the percent collagen, which determined by relative collagen production against total protein production, w3s decreased from $7\%\;to\;3.6\%$. This inhibitory effect of substance P on collagen production was disappeared when cells were treated concomitantly with indomethacin. It means that substance P-induced inhibitory effect on collagen production was due at least in part to the production of prostaglandins. To evaluate whether substance P-induced inhibitory effect on collagen production is correspond to the steady-state levels of procollagen mRNA, Northern blot hybridization was performed and it showed that substance P has no effect on the steady-slate level of ${\alpha}1(I)$ procollagen mRNA. It means that the inhibitory effect of substance P on collagen production was due to the change of a certain mechanism after posttranscription. In this context, gelatinase production by substance P in periodontal ligament cells was evaluated by zymography. Zymogram showed that substance P has no effect on gelatinase production in periodontal ligament cells. To explore wheter substance P-induced inhibitory effect on collagen production is selevtive in periodontal ligament cells or not, MC3T3-E1 cells which originated from mouse calvaria was used. It showed that substance P has no effect on collagen production in MC3T3-E1 cells. Taken together, substance P inhibits collagen production in human periodontal ligament cells. This effect was not due to the change of the steady-state level of procollagen mRNA and gelatinase production, but due at least in part to the change of prostaglandins production.

• Korean Journal of Animal Reproduction
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• v.25 no.2
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• pp.125-130
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• 2001

This study was performed to report a direct dose dependent stimulatory effect of the Flavonoid(F) on basal testosterone secretion and a dose dependent effect on LH induced testosterone production by Leydig cell of matured rats in vitro culture. F was obtained kom the Rhus vernicifua through aceton extraction and silica gel adsorption column chromatography. Leydig cells (1$\times$10$^{6}$ cells/well) from 12 weeks old rats were incubated with or without F(0, 20, 40, 80, 160 ng) or insulin-like growth factor-I(IGF-I) in the presence or absence of LH(10, 100ng). 1. The maximal stimulatory concentrations of testosterone in culture media were showed at 24hr of culture. but these testosterone level were decreased at 36 hr of culture. 2. Flavonoid(80ng) were significantly(P ＜ 0.05) increased testosterone production compared with control groups for 12 hr culture. 3. Testosterone secretion by Leydig cells stimulated with LH(10, 100ng) for 6 hr and 12hr culture compared with 3 hr culture. 4. LH 10 ng augmented testosterone were increased by addition of F 40 ng for 12 hr culture. 5. F(0 and 40 ng) also enhanced LH 10 ng stimulated testosterone for 3 hr Leydig cells culture. 6. Addition of IGF-I 100 ng to the culture medium for 6 hr were increased the concentration of testosterone by Leydig cells stimulated with 100 ng LH. These results indicate that Flavonoid has a direct stimulatory effect on basal testosterone secretion in rat Leydig cells, and also modulates LH mediated testosterone. Therefore, Flavonoid may act as a modulator on gonadal development or gonadal steroidogenesis in direct or indirect.

• The Journal of Korean Society for Radiation Therapy
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• v.16 no.1
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• pp.29-37
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• 2004

Purpose : A rectum and a bladder should be carefully considered in order to decrease side effects when HDR patient of uterine cervix cancer. Generally speaking, the value of dosimeter at a rectum and a bladder only depends on the value of a planning equipment, while some analyses of the value of dosimetry at rectum with TLD has been reported Or the contrary, it is hardly to find a report with in vivo dosimetry(diode detector). On this thesis, we would like to suggest the following. When a patient of uterine cervix cancer is in therapy, it is helpful to put a diode detector inside of a rectum in order to measure the rectal dose Based upon the result of the dosimetry, the result can be used as basic data at decreasing side effects. Materials and Methods : Six patients of uterine cervix cancer(four with tandem and ovoid, one with cylinder, and the other one with tandem and cylinder) who had been irradiated with HDR. Ir-192 totally 28 times from February 2003 to June 2003. We irradiated twice in the same distant spots with anterior film and lateral film whenever we measured with a diode detector. Then we did planning and compared each film. Results : The result of the measurement 4 patients with a diode detector is the following. The average and deviation from 3 patients with tandem and ovoid were $274.1{\pm}13.4cGy$, from 1 patient with tandem and ovoid were $126.1{\pm}7.2cGy$, from 1 patient with cylinder were $99.7{\pm}7.1cGy$, and from 1 patient with tandem and cylinder were $77.7{\pm}11.5cGy$. Conclusion : It is difficult to predict how the side effect of a rectum since the result of measurement with a diode detector depends on the state of a rectum. According to the result of the study, it is effective to use a TLD or an in vivo dosimetry and measure a rectum in order to consider the side effect. It is very necessary to decrease the amount of irradiation by controlling properly the duration of the irradiation and gauze packing, and by using shield equipments especially when side effects can be expected.

• Progress in Medical Physics
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• v.24 no.4
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• pp.315-322
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• 2013

The aim of this work is to verify the self-quality assurances in medical institutions in Korea through the external audits by the group of experts and have a mutual discussion of the systematic problems. In order to validate the external audits 30 of 80 medical institutions across the nation were picked out considering the regional distribution and the final 25 institutions applied voluntarily to take part in this work. The basic rules were setup that any information of the participants be kept secrete and the measurements be performed with the dosimetry system already verified through intercomparision. The outputs for 2 or more photon beams, the accuracy of gantry rotation and collimator rotation and the poistional accuracy of MLC movement were measured. The findings for the output measurement showed the differences of -0.8%~4.5%, -0.79%~3.01%, and -0.7%~0.07% with respect to that of the verified dosimetry system for the 6MV, 10MV, and 15MV, respectively. For the reference absorbed dose 8 (16%) of 50 photon beams in 25 medical institutions differed 2.0% or greater from the reference value. The coincidences of Field size with x-ray beam and radiation isocenters of Gantry roration and collimator rotation gave the results of within ${\pm}2$ mm for every institute except 2 institutions. The positional accuracy of MLC movement agreed to within ${\pm}1$ mm for every institute. For the beam qualities of 6 MV photon beams kQ values showed the distribution within 0.4% between maximum and minimum. For the protocols 21 institutions (84%) used absorbed dose to water based protocol while 4 insitutions (16%) used air kerma based one. 22 institutions employed the SSD technique while 3 institutions did the SAD one. External audit plays an important role in discovering the systematic problems of self-performing Quality Assurances and having in depth discussion for mutual complementation. Training experts of international level as well as national support system are required so that both the group of experts of medical physicists and government laboratory could perform together periodical and constant external audits.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.26 no.1
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• pp.149-162
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• 2000

Coenzyme Q10 is found in all tissues including skin and it is the well-known coenzyme for mitochondrial enzymes. The electron and proton transfer functions of the quinone ring are of fundamental importance for the oxidative phosphorylation pathway to generate energy in the cells. Coenzyme Q10 has been studied as a potent antioxidant molecule in the skin. It is involved in the skin's response to UVR irradiation. The concentration of this antioxidant in UVR exposed skin is higher than in non-exposed skin. However, recent studies have also shown that coenzyme Q10 is one of the first antioxidants to be depleted when skin is UVR-irradiated. This indicates that coenzyme Q10 is primarily involved in defense mechanisms of the skin. Therefore, we questioned whether coenzyme Q10 shows reulatory effect of melanogenesis. Here we report that coenzyme Q10 inhibits melanin neosynthesis of normal human melanocytes grown in culture, and lightens UVB-induced hyperpigmentation of the guinea pig skin in vivo. We treated human melanocytes with 0.05mM to 0.5mM of coenzyme Q10 for a total of two days. This inhibited melanin neosynthesis of cultured human melanocytes dose-dependently. The inhibitory effect of coenzyme Q10 was as effective as kojic acid or vitamin C on cultured human melanocytes. CoQ10 didn't have direct inhibitory effect on tyrosinase activity in in vitro tyrosine hydroxylase activity To further clarify the effect of coenzyme Q10 on the melanogenesis, we established UVB-induced hyperpigmentation on the shaved backs of brownish guinea pigs. The UVB intensity was 500mJ/$\textrm{cm}^2$ and the total energy dose was 1,500 mJ/$\textrm{cm}^2$. The animals were exposed to UVB radiation one times a week for three consecutive weeks. Coenzyme Q10, kojic acid, Arbutin, vitamin C(1% in vehicle) or vehicle alone as a control were then topically applied daily to the hyperpigmented areas twelve times per week far four successive weeks. The lightening effect was evaluated by visual scoring, chromameter and immunohistochemistry. Coenzyme Q10 had lightening effect on the UVB-induced hyperpigmentation without any other side effects, whereas another compounds showed weak lightening efficacies. Therefore, these results suggest that coenzyme Q10 may be useful for solving physiological hyperpigmenting problems for cosmetic purposes.