• Title/Summary/Keyword: time course toxicity

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Can Capecitabine be used Instead of Concurrent Bolus 5-FU in Postoperative Chemoradiotherapy for Gastric Adenocarcinoma?

  • Yoney, Adnan;Isikli, Levent
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5127-5131
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    • 2013
  • Background: 5-fluoro-uracil (FU) is a common agent in postoperative chemoradiation in gastric adenocarcinoma. However, FU is not well tolerated in a significant proportion of patients. Capecitabine (CA) is an orally administered fluoropyrimidine carbamate which is preferentially converted to active 5-FU and is one of the agents used instead of FU in such cases. We compared the toxicity, local and distant control and survival rates with FU or oral CA during the course of concurrent radiotherapy to assess the role of CA used instead of FU. Materials and Methods: We conducted an analysis of survival, disease control and toxicity data in 46 patients treated with postoperative chemoradiation following total or subtotal gastrectomy for gastric adenocarcinoma with either FU or CA between January 2008 and December 2012. Results: Median follow-up was 19 months (range: 3-59), median survival time was 23 ({\pm}6.08) months and 1-3 years overall survival (OS) rates were 64.9-39% for all patients. Compared with the CA regimen, the incidence of treatment interruption was higher with FU (p=0.023), but no significant differences were seen in local control (p=0.510), distant recurrences (p=0.721) and survival rates (p=0.866) among patients. Conclusions: Concurrent CA with radiotherapy seems to be a more tolerable and an equally effective regimen for the postoperative treatment of gastric adenocarcinoma when compared to FU.

Long-term Fistula Formation Due to Retained Bullet in Lumbar Spine after Gunshot Injury

  • Jeon, Se-Il;Im, Soo Bin;Jeong, Je Hoon;Cha, Jang Gyu
    • Journal of Trauma and Injury
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    • v.30 no.2
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    • pp.51-54
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    • 2017
  • We here report a case of long-term fistula formation due to bullet retention for 30 years in the lumbar spine after a gunshot injury, and describe its treatment. A 62-year-old male visited our hospital due to pus-like discharge from his left flank. The discharge had been present for 30 years, since his recovery from an abdominal gunshot injury. A spine radiography showed radiopaque material in the body of the third lumbar vertebra. Foreign body was removed using an anterolateral retroperitoneal approach. The postoperative course was uneventful. The patient was discharged 7 days after the operation and was followed-up for 8 months, during which time, the fistula did not reoccur. A bullet retained long term in the vertebral body may cause obstinate osteomyelitis and fistula formation. A fistula caused by a foreign body in the spine can be effectively treated by surgical removal.

Monitoring fibrillation of the pathogenic huntingtin protein using NMR

  • Seo, Min-Duk
    • Journal of the Korean Magnetic Resonance Society
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    • v.24 no.2
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    • pp.43-46
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    • 2020
  • Huntington's disease (HD) is an inherited neurodegenerative disease caused by abnormal polyglutamine (polyQ) expansion in the huntingtin protein (Htt). There is no cure for HD so far. Although exact molecular mechanism of HD pathogenesis is still elusive, fibril formation of the expanded Htt is linked to the toxicity. In this study, we prepared the expanded Htt containing 46 glutamines, and induced the fibrillation by proteolytic cleavage. Fibrillation of the pathogenic Htt has been monitored by time course NMR experiment. The NMR-based monitoring method could be widely used to screen the candidates to inhibit the fibrillation of the pathogenic Htt.

Purification and partial characterization of bacillus thuringiensis var.thuringiensis exotoxin (Bacillus thuringiensis var. thuringiensis가 생산하는 .betha.-exotoxin의 정제와 특성)

  • 심창범;이형환;이희무
    • Korean Journal of Microbiology
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    • v.23 no.4
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    • pp.271-281
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    • 1985
  • Bacillus thuringiensis var. thuringiensis produces an extracellular insecticidal thermostable .betha.-exotoxin, which was purified through microfiltering, barium precipitation, charcoal absorption chromatography, ion exchange column chromatography and gel filtration. The exotoxin in each purification step was detedted by thin layer chromatography, high pressure liquid chromatography and paper electrophoresis with efficient results. The exotoxin productivity on time course was checked by spectrophotometric absorbance at 258nm with the result that the exotoxin was initially produced in 6 hour culture and reached maximum value in 36 hour culture. Anti-bacterial effect test on Micrococcus flava was applied as toxicity test. The results showed that frowth inhibition of M. flava could be shown in plate assay of cell free filtered supernatant, alkaline eluant from charcoal and purified exotosin obtained from gel filtration column chromatography on Sephadex G-10 appeared to be 740. Heat stability of the exotoxin was confirmed through autoclaving twice.

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Short-course palliative radiotherapy for uterine cervical cancer

  • Kim, Dong Hyun;Lee, Ju Hye;Ki, Yong Kan;Nam, Ji Ho;Kim, Won Taek;Jeon, Ho Sang;Park, Dahl;Kim, Dong Won
    • Radiation Oncology Journal
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    • v.31 no.4
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    • pp.216-221
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    • 2013
  • Purpose: The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Materials and Methods: Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. Results: The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Conclusion: Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

16 Cases of Anti-obesity Drug Intoxication Experienced in 4 Emergency Departments (4개 응급센터에 내원한 비만치료제 중독 환자들의 다양한 임상양상 경험: 16례)

  • Han, Sung Hoon;So, Byung Hak;Jung, Won Joong;Kim, Hyung Min
    • Journal of The Korean Society of Clinical Toxicology
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    • v.10 no.2
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    • pp.111-117
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    • 2012
  • Purpose: In Korea, few studies have examined the acute toxicity of anti-obesity drugs. The purpose of this study is to analyze the general characteristics and clinical aspect of acute anti-obesity drug intoxication. Methods: We retrospectively investigated patients admitted to the emergency department after anti-obesity drug intoxication between March, 2004 and February, 2012. The medical records of these patients were reviewed for demographic data, toxicologic history, time elapsed to presentation, clinical symptoms and signs, treatment, and outcome. Results: There were a total of 18 anti-obesity intoxication cases during the study period; of 16 which were included in our study. The purchasing route of the anti-obesity drug was mainly through a doctor's prescription (68.8%), however, some were obtained through the internet and the pharmacies. The mean time to The most commonly ingested antiobesity drug was sibutramine (31.3%) and many of the cases (62.5%) were multi-drug ingestions. The most common clinical manifestations were gastrointestinal symptoms (94%), but, CNS symptoms (75%) and cardiovascular symptoms (75%) were almost equally present. 13 patients (81%) were discharged after clearance of toxic symptoms and signs with a mean observational period of 7.0 hours. 3 patients were admitted for observation and treatment; of which 1 patient died due to fatal complications. Conclusion: Most anti-obesity intoxications show mild toxicity and a nonfatal clinical course. However, the recent trend toward prescribing psychostimulant anti-obesity medication, which can be fatal after an acute overdose, calls physicians' attention to treating of anti-obesity intoxications.

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Clinical Study on Lobaplatin Combined with 5-Fu and Concurrent Radiotherapy in Treating Patients with Inoperable Esophageal Cancer

  • Jia, Xiao-Jing;Huang, Jing-Zi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6595-6597
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    • 2015
  • Objective: To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophageal cancer. Methods: Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectively analyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu ($500mg/m^2$) injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time, late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patients were firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4Gy). Results: All patients completed treatment, including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and 3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months. The adverse reactions included myelosuppression, which was mainly degree I and II. The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Conclusion: Lobaplatin plus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advanced stage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.

A Study on the Preventive Effect of Extract of Glycyrrhizae Radix and Glycine Semen on NAC Intoxication (Carbamate 중독에 대한 감초, 흑두 추출액의 예방효과에 관한 연구)

  • 신일순;민경진;강회양
    • Journal of Environmental Health Sciences
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    • v.19 no.2
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    • pp.61-68
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    • 1993
  • This study aimed at evaluating the preventive effect of Glycyrrhizae Radix and Glycine Semen Extract (GGE) against NAC intoxication. NAC is widely used pesticide in many countries and derivative of carbamats and GGE is well-known antidote to some kinds of toxicants which was referenced from oriental medicine text. The results obtained were as follows: 1) After injecting NAC (100,140 mg/kg), determined Ch.E activities decrease 44.77~50.86% for all experimental groups at one hour after exposure, and were gradually recovered in the course of time. 2) In toxicity test of GGE, there were no sign of death or poisoning up to 5000 mg/kg of GGE for p.o. in mice. From this, we suggest that the LD$_{50}$ of GGE would be above 5000 mg/kg. 3) The Ch.E activity in control group was 471.43 $\pm$ 4.85 luff, group I was 215.27 $\pm$ 23.13 IU/l, group II and group III were 304.03 $\pm$ 9.03 IU/l, 433.81 $\pm$ 21.73 IU/l, respectively. Compare to the control group with experimental group I, remarkable difference revealed (p< 0.01), but the Ch.E activities of group II and III were similar to those of control group. This is indicate that GGE possess a potent activity of recovering Ch.E. GGE had a very remarkable preventive effect on NAC toxicity, and it was able to know that Ch.E activity dramatically increased according to GGE dosage increasing. 4) When GGE and NAC were administered by p.o. simultaneously, LD$_{50}$ and confidence intervals of each group were as follows: the control group: 270 mg/kg, 234.99~310.23 mg/kg, group I and II (GGE 500 mg/kg, 1000 mg/kg by p.o.): 310 mg/kg, 271.69~353.71mg/kg, and 325 mg/kg, 285.09~370.50 mg/kg, respectively. In the comparison with the control group, the protective index was 1.1 and 1.2, respectively. From the above result, GGE has reactivation effect to decreasing Ch.E activity induced by exposure to NAC. Furthermore, GGE shows a preventive effect on NAC intoxication.

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Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma

  • Pathy, Sushmita;Kumar, Lalit;Pandey, Ravindra Mohan;Upadhyay, Ashish;Roy, Soumyajit;Dadhwal, Vatsla;Madan, Renu;Chander, Subhash
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.5075-5079
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    • 2015
  • Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco-regional control with a conventional schedule. Materials and Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin $40mg/m^2$. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin $20mg/m^2/day$ was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were $65{\pm}12$ and $48{\pm}4$ days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade ${\geq}3$ toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.

Differential Role of Ethanol, Glycerol, 4-Methylpyrazole and Isoniazid on Human CYP2E1 Activity in Intact HepG2 Cells (HepG2 세포에서 Ethanol, Glycerol, 4-Methylpyrazole 및 Isoniazid에 의한 Human CYP2E1 활성변화)

  • 최달웅
    • Toxicological Research
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    • v.19 no.3
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    • pp.235-240
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    • 2003
  • The modification of CYP2E1 activity is of considerable interest because of its role in the metabolic activation of a variety of toxic chemicals. In the present studies, the time-course of changes in human CYP2E1 activities was determined after treatment with ethanol, glycerol, 4-methylpyrazole or isoniazid using intact HepG2 cells transfected by human CYP2E1. Hydroxylation of chlorzoxazone was chosen for the measurement of CYP2E1 activity. CYP2E1 protein levels were increased upon cultivation of cells in the presence of ethanol, glycerol, 4-methylpyrazole or isoniazid for 24 hr. After 24 hr cultivation, ethanol or glycerol increased CYP2E1 activities, whereas 4-methylpyrazole or isoniazid inhibited. This different effect of the chemical inducers on CYP2E1 activi-ties persisted to subsequent 24 hr. Competitive inhibition study suggested that 4-methylpyrazole or isoniazid has stronger binding affinity to CYP2E1 than ethanol or glycerol. These results demonstrate that different binding affinity of the chemical inducers to the active site of CYP2E1 plays important role in determining real CYP2E1 activity in intact cells after treatment with the chemical inducers. Present study would be helpful in precise understanding of human CYP2E1-mediated toxicity.