• Journal of Radiation Protection and Research
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• 제10권2호
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• pp.122-129
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• 1985

S-2, W-diaminopentyl isothiuronium bromide 및 그 thiophosphate 유도체는 phthalimide 또는 l-ornithine 산(酸)으로부터 출발(出發)하여 합성(合成)되었다. 합성(合成)한 isothiuronium bromide 및 S-2-(W-aminoalkylamino)ethyl isothiuronium bromide의 약독성(藥毒性)을 체중(體重) 25-35g, $4{\sim}8$주생(週生) ICR 생쥐를 사용(使用)하여 검사(檢査)하였다. 그 결과(結果) 전자(前者)의 화합물(化合物)이 후자(後者)의 것들보다 약독성(藥毒性)이 약(弱)하다는 것이 판명(判明)되었다. 이와같은 약독성(藥毒性)의 차이(差異)는 화합물(化合物)들의 화학구조(化學構造)의 차(差)에 기인(起因)하는 것으로 보였으며 IR 분광분석법(分光分析法)으로 그 내용(內容)이 검토(檢討)되었다. 이들 화합물(化合物)의 방사선장해방호효과에 관(關)하여 현재(現在)까지의 관련(關聯)된 연구(硏究)문헌에 대한 고찰을 하였으며 diaminopentyl 유도체들은 약독성(藥毒性)이 비교적 낮고 좋은 방사선장해방호화합물(放射線障害防護化合物)인 것으로 사려된다.

• 한국임상약학회지
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• 제12권1호
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• pp.1-6
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• 2002

Central Cancer Registry of Korean National Cancer Center in 1999 reported that mortality from lung cancer is higher than mortality from stomach cancer or hepatocellular carcinoma in Korean male. Lung cancer is classified into small cell cancer and non-small cell lung cancer (NSCLC), and NSCLC patients account for $70\%$ of the whole lung cancer patients. The purpose of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination in Korean patients with NSCLC. All patients who had received the combination therapy of docetaxel and cisplatin for histologically confirmed NSCLC in Ajou University Hospital between 2000. $2\~2001$. 4 were retrospectively evaluated for the responses and toxicities of that combination therapy. Nineteen patients were treated with docetaxel 75 $mg/m^2$ on Day 1 and cisplatin 25 $mg/m^2$ on Day 1-3 every 4 weeks. The response for combination regimen was evaluated by CT scans after 2 or 3 cycles of treatments. Seventeen patients were evaluated for the responses and the 19 patients far the toxicities. Among the 19 patients (14 men and 5 women), there were one patient $(5.3\%)$ with stage I disease, 4 patients $(21.1\%)$ with stage III disease, and 14 patients $(73.1\%)$ with stage IV disease. Of the 17 patients who were evaluable for response, complete response (CR) was not observed in any patient while partial response (PR) was observed in 5 patients $(29.4\%)$. The overall response rate (CR+PR) was $29.4\%$. Stable disease (SD) was observed in 11 patients $(64.7\%)$ and progressive disease (PD) in 1 patient $(5.9\%)$. The toxicities were graded by NCI (National Cancer Institute) Common Toxicity Criteria for the evaluable 70 cycles. Grade 3 or 4 neutropenia occurred in 53 cycles $(76\%)$. Four patients were hospitalized due to febrile neutropenia. The combination chemotherapy of docetaxel and cisplatin was effective as NSCLC treatments, however, the regimen must be administered carefully due to its hematological side effects.

• 대한수의학회지
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• 제35권3호
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• pp.437-445
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• 1995

과일 및 채소류의 곰팡이 억제제로 개발된 captafol은 인간 및 동물에서의 독성작용은 많이 보고된 바 있으나 이들의 독작용을 완화시키거나 치료할 수 있는 제제에 대한 연구는 별로 알려진 바 없다. captafol에 의한 혈액학 및 혈청 생화화적 변화에 따른 cysteine의 방어 작용을 확인할 목적으로 랫트에 5mg/kg 용량의 captafol을 1회 복강 투여하고 동시에 5, 58, 290 및 580mg/kg cysteine을 각각 투여하고 체중의 변화, 부검소견, 절대장기중량, 혈액학 및 혈청 생화학적 소견을 비교 분석 하였다. captafol 단독 투여군에서는 체중 및 간 장기중량 감소, 복강내 장기들의 섬유소에 의한 유착 및 복수 등이 현저하였으며 적혈구 수, hemoglobin 농도, 혈청 AST의 증가가 인정되었으며 또한 혈청 인지질 함량 감소가 확인되었다. 한편, cysteine 58mg/kg 이상의 용량군에서는 복강내 장기들의 유착 및 복수가 확인되지 않았으며 장기중량, 혈액학 및 혈청 생화학적 소견에서도 정상을 나타내었다. 이 연구 결과는 captafol의 중독증상에 대해 cysteine 및 sulfhydryl군을 가진 물질은 그 증세를 감소시키거나 완화시킬 수 있는 효과가 있음을 보여주고 있다.

• 한국환경보건학회지
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• 제47권5호
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• pp.462-471
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• 2021

Background: The number of synthesized chemicals has rapidly increased over the past decade. For many chemicals, there is a lack of information on toxicity. With the current movement toward reducing animal testing, the use of toxicity big data and deep learning could be a promising tool to screen potential toxicants. Objectives: This study identified potential chemicals related to reproductive and estrogen receptor (ER)-mediated toxicities for 1135 cleaning products and 886 laundry products. Methods: We listed chemicals contained in cleaning and laundry products from a publicly available database. Then, chemicals that potentially exhibited reproductive and ER-mediated toxicities were identified using the European Union Classification, Labeling and Packaging classification and ToxCast database, respectively. For chemicals absent from the ToxCast database, ER activity was predicted using deep learning models. Results: Among the 783 listed chemicals, there were 53 with potential reproductive toxicity and 310 with potential ER-mediated toxicity. Among the 473 chemicals not tested with ToxCast assays, deep learning models indicated that 42 chemicals exhibited ER-mediated toxicity. A total of 13 chemicals were identified as causing reproductive toxicity by reacting with the ER. Conclusions: We demonstrated a screening method to identify potential chemicals related to reproductive and ER-mediated toxicities utilizing chemical toxicity big data and deep learning. Integrating toxicity data from in vivo, in vitro, and deep learning models may contribute to screening chemicals in consumer products.

• 한국환경보건학회지
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• 제47권5호
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• pp.446-453
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• 2021

Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

• 대한두경부종양학회지
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• 제38권2호
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• pp.7-13
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• 2022

Human papillomavirus (HPV) is a causative agent for a subset of oropharyngeal cancer (OPC). The current standard of care (SOC) for locally advanced OPC is 70 Gy definitive radiotherapy (RT) concurrent with cisplatin, which entails significant proportions of acute and late grade 3 or higher toxicities. Accordingly, discovery of favorable prognosis of HPV-related OPC has led to enthusiasm to attenuate subspecialties therapy in multidisciplinary treatment. Diverse deintensification strategies were investigated in multiple phase 2 trials with an assumption that attenuated treatments result in comparable oncologic outcome and less toxicities compared with SOC. Several trials on chemotherapy deintensification revealed that concomitant administration of cisplatin is not to be omitted or substituted for cetuximab without compromising progression-free survival or local control. A transoral robotic surgery (TORS) is investigated as alternative local treatment, but TORS plus SOC or mild deintensified adjuvant RT showed similar toxicities and inferior oncologic outcomes compared with SOC definitive RT or moderately deintensified RT. However, it has been reported that TORS plus deintensified 30-36 Gy adjuvant RT results in excellent outcome and less late toxicity compared with SOC adjuvant RT. Several phase 2 trials reported apparently equivalent progression-free survival and local control and similar adverse effects with moderately deintensified 60 Gy RT compared with SOC 70 Gy RT. Further dose reduction below 60 Gy has been investigated using biology-directed approaches, which use response to induction chemotherapy or metabolic images to triage HPV-positive OPC for deintensified RT. In summary, these trials provide valuable insights for future directions. Available evidence consistently showed that moderately deintensified RT is effective and safe for HPV-positive OPC in both definitive and adjuvant settings. Concurrent cisplatin remains an essential component without which progression-free survival is significantly compromised for advanced HPV-positive OPC. A simple incorporation of TORS to SOC may be detrimental for oncologic outcome without anticipated toxicity reduction. Given the lack of level 1 evidence, it is prudent to curb an unjustified deviation from the current SOC and limit any deintensified strategies to clinical trials and adhere to the current SOC.

• Radiation Oncology Journal
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• 제32권2호
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• pp.57-62
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• 2014

Purpose: To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods: Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results: Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ${\geq}$ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion: The cumulative rectal dose in EQD2 >65 Gy have association with ${\geq}$ grade 2 LENT-SOMA scale.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.867-870
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• 2001

아급성 독성 시험으로부터, 미립구내의 레티노익 산을 기준으로 한 투여량이 100mg/kg 일때는 4마리의 치사 개체가 보이는 등의 심각한 독성 효과가 유발되었으며, 25 및 50mg/kg인 경우에 독성 효과가 거의 나타나지 않음을 관찰하였다. 50mg/kg의 투여량의 경우, 일부 동물에서 뼈골절 현상이 나타났지만, 이러한 독성효과는 항염증제를 같이 투여함으로써 극복될 수 있을 것으로 생각되어졌다. 따라서, 앞으로의 실험에서는 항염증제를 이용하여, 가능한 독성을 억제하연서, 보다 빠른 기간 내에 상태가 회복될 수 있도록 하는 연구를 행할 것이다.

• 한국응용곤충학회지
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• 제19권2호
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• pp.79-83
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• 1980

야외에서 채집한 거세미나방(Agrotis fucosa Butler) $1\~6$령충에 대한 5개 토양살충제를 국소처리하여 $LD_{50}$치를 구하여 령충별 독성과 내성을 비교 검토하였다. 유충의 령기가 진행됨에 따라 $LD_{50}$치가 현저히 증가하였으며 그 차이는 약제의 종류에 따라 차이가 현저하였는데 그 독성은 phoxim $(Volaton^{(R)})$이 가장 높았고 다음이 carbofuran$(Curaterr^{(R)})$, chlorpyrifos $(Dursban^{(R)})$ Mocap, diazinon의 순위였다. 그리고 $1\~2$령충까지의 $LD_{50}$치는 비교적 낮았으나 3령충부터 $LD_{50}$치는 급격히 증가하였다. (2) 령충별 내성비($2\~6$령충의 $LD_{50}$/1령충의의 $LD_{50}$)에 있어서 phoxim은 $11.1\~251.6$배, diazinon은 $1.2\~126.6$배, chlorpyrifos는 $4.3\~97.5$배, carbofuran은 $1.6\~44.3$배, Mocap은 $11.5\~18.7$배로서 령기가 진행됨에 따라 약제에 대한 내성이 크게 증가하였으며 그 정도는 약제의 종류에 따라 차이가 있었다. (3) diazinon에 대비한 phoxim, carbofuran, chlorpyrifos, Mocap의 령충별 독성비는 3령충까지는 낮거나 높아 일관성이 없었으나 4령에서 6령까지는 대조약제 diazinon에 비하여 모드 높은 독성비를 나타내었다. 1령충에서 6령충까지의 평균 독성비(각 령충별 $LD_{50}$치 기준)는 diazinon에 대하여 phoxim은 5.2배 carbofuran은 1.9배 chlorpyrifos는 1.7배, Mocap은 1.1배 이었다.

• 대한두경부종양학회지
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• 제27권1호
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• pp.47-53
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• 2011

Purpose : Concurrent chemoradiotherapy(CCRT) with 3 weekly cisplatin is the standard treatment of locally advanced head and neck cancer(HNC). The aim is to evaluate the efficacy and toxicities of low-dose weekly cisplatin-based CCRT, which was devised to reduce the toxicity of CCRT. Method : We retrospectively analyzed HNC patients who received low-dose weekly cisplatin-based CCRT between 2008 and 2010. Cisplatin 35mg/$m^2$ was weekly given to all patients during radiotherapy. The efficacy was evaluated by the degree of clinical response, treatment failure and survival. The toxicity was evaluated by hematologic toxicities and oral mucositis. Results : A total of 27 patients were analyzed and median age was 59(range 31-81). The ratio of administered dose of radiotherapy and cisplatin to planned dose were 0.98 and 0.93, respectively. Complete remission and partial remission were 73% and 23%, respectively. Treatment failure was observed in 8(30%) patients. 1-year survival rate and 1-year disease free survival rate were 82% and 59%, respectively. Overall survival and progression-free survival did not reach median time. Grade 3/4 anemia, neutropenia, thrombocytopenia and oral mucositis were observed in 11%, 19%, 7% and 32% of patients, respectively. In terms of administered cycles, however, only 1-3% of grade 3/4 hematologic toxicities occurred among total 190 cycles. Severe oral mucositis were statistically associated with old age(p=0.003). Treatment failure had no statistical relation with age, pathology, primary site and stage. Conclusion : Low-dose weekly cisplatin-based CCRT seemed to deliver enough dose of cisplatin and to show low drop-out rate and good efficacy with low hematologic toxicities.