• Proceeding of EDISON Challenge
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• 2017.03a
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• pp.677-687
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• 2017

Caffeine has a long history of human consumption but the consumption of caffeine due to caffeinated energy drinks(CEDs) is rapidly growing. Marketing targets of CED sales are children, adolescents and young adults, possibly caffeine-sensitive groups and its effect for them can be significantly different from healthy adults. Caffeine-related toxicities among these groups are growing in number and a number of countries are recognizing severity of caffeine toxicities. Previous research showed prediction of maximal plasma caffeine concentration profiles after the single CED ingestion and the primary aim of this study is to visually predict plasma caffeine concentration after the single and multiple ingestion of standard servings of CED. Based on the population pharmacokinetic model using Monte Carlo simulation, prediction of caffeine concentration leading to caffeine intoxication in the sensitive groups is quantitatively presented and visualized. This research also broadens the perspective by creating and utilizing diverse open science tools including R package, Edison Science App and Shiny apps.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.210-215
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• 2011

Imatinib mesylate, a selective inhibitor of BCR-ABL kinase activity, has demonstrated significant clinical efficacy in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). It has become the standard of treatment for these diseases. Although the toxicity profile of imatinib is superior to that of interferon or other cytotoxic agents, some adverse events including edema, gastrointestinal toxicities and hematologic toxicities are commonly observed in the patients treated by imatinib. We present two cases of imatinib induced interstitial pneumonitis during the treatment of a chronic phase of CML.

• Journal of Environmental Health Sciences
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• v.35 no.6
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• pp.433-446
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• 2009

Pharmaceuticals in the aquatic environment are trace contaminants of growing importance in environmental health due to their physiologically active nature. Pharmaceuticals could affect non-target species and might eventually damage sustainability of susceptible populations in the ecosystem. Potentials for health consequences among susceptible human population cannot be ruled out since long-term exposure to cocktails of pharmaceuticals, which might be present in drinking water, is possible. Selection of antibiotic resistant microorganisms is of another concern. In order to understand, and if needed, to properly address the environmental health issues of pharmaceutical residues, knowledge gaps need to be filled. Knowledge gaps exist in many important areas such as prioritization of target pharmaceuticals for further risk studies, occurrence patterns in different environments, chronic toxicities, and toxicities of pharmaceutical mixtures. Appropriate treatment technologies for drinking water and wastewater could be developed when they are deemed necessary. One of the simplest, yet most efficient measures that could be undertaken is to implement a return program for unused or expired drugs. In addition, implementation of environmental risk assessment frameworks for pharmaceuticals would make it possible to efficiently manage potential environmental health problems associated with pharmaceutical residues in the environment.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.243-245
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• 2016

The insecticidal toxicities of seven essential oils against Ricania sp. nymph and adults, newly recorded pest, were evaluated using leaf-dipping and spray methods. At 72 h exposure time, the $LC_{50}$ values of the essential oils of Artemisia vulgaris, Anethum graveolens, Citrus paradisi, Melaleuca alternifolia, Melaleuca leucadendron, Neroli bigarade and Tagetes erecta were 251.02, 387.31, 286.21, 353.54, 275.64, 424.55, $165.68mg/cm^2$ when using the leaf dipping method against Ricania sp. nymphs, and 278.31, 402.11, 306.11, 379.64, 298.22, 459.56, $183.21mg/cm^2$ when using the spray method against Ricania sp. adults, respectively. These results indicate that the essential oil of the Tagetes erecta can be potentially used as new natural insecticidal agents against Ricania sp. nymph and adults.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.208-216
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• 2017

Purpose: To evaluate the feasibility of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional conformal radiotherapy (3D-CRT). Materials and Methods: Patients who were treated with PCRT for LARC from 2015 January to 2016 December were retrospectively enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine. Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of additional chemotherapy was administered. Pathologic tumor responses were compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal, genitourinary, hematologic, and skin toxicities were compared between the two groups based on the RTOG toxicity criteria. Results: SIB-IMRT was used in 53 patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000), pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0 resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but gastrointestinal toxicities were not different across the two groups. Conclusion: SIB-IMRT showed lower GU toxicity and similar tumor responses when compared with 3D-CRT in PCRT for LARC.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.257-267
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• 2017

Purpose: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. Materials and Methods: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. Results: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46-110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90-42.56). Conclusion: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.129-138
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• 2018

Purpose: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ${\leq}3cm$ in size. Materials and Methods: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. Conclusions: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.903-915
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• 1996

Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The liming, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks 10 the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration : Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was nor different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicities, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group (p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.