• Journal of Radiation Protection and Research
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• v.10 no.2
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• pp.122-129
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• 1985

S-2, W-diaminopentyl isothiuronium bromide and relevant thiophosphate derivative were prepared starting from both phthalimide and l-ornithinic acid. Drug toxicities of the prepared isothiuronium bromide and S-2-(W-aminoalkylamino) ethyl isothiuronium bromides were tested through ICR male mice, 4 and 8 weeks old and weighing $25{\sim}35g$. The former compound was found to be less toxic than those of latter compounds. This difference of drug toxicities seemed to be originated from their chemical structures, which were examined through IR Spectrometry Radioprotective effects of these compounds were discussed through relevant research data and diaminopentyl derivatives are considered to be a potent radioprotectant with low drug toxicity.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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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.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.437-445
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• 1995

This experiment was carried out to study the preventive effect of cysteine on the toxicities of captafol to the hematological and serum biochemical values. A single dose of captafol(5mg/kg BW, ip) was given to male Sprague-Dawley rats and its toxicities were evalutated by body weitht changes, autopsy findings, absolute organ weight, and hematological and serum biochemical parameters. The single dose of captafol caused significant decreases in body weitht, and absolute liver weight, as-cites, fibrin clot in abdominal cavity, adhesion of liver lobes significant elevation of number of RBC, hemoglobin concentration and serum AST activity, and decreased of serum phospholipid level. Where as cysteine(over 58mg/kg BW) given immediately after captafol appeared to prevent the ascites, fibrin clot in abdominal cavity and liver lobe adhesion. It also prevented the liver and blood, especially RBC toxicites. The results suggest that cysteine and other compounds containing sulfhydryl groups may protect the subjects from captafol-induced toxicity.

• Journal of Environmental Health Sciences
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• v.47 no.5
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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.

• Journal of Environmental Health Sciences
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• v.47 no.5
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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.

• Korean Journal of Head & Neck Oncology
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• v.38 no.2
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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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• v.32 no.2
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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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• 2001.11a
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• pp.867-870
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• 2001

All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

• Korean journal of applied entomology
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• v.19 no.2 s.43
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• pp.79-83
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• 1980

The toxicities of some soil insecticides were evaluated in terms of the tolerance to various larval-ins tars of the common cutworm (Agrotis fucosa Butler) using topical application method in the laboratory. $LD_{50}$ values(ug/larva) were determined by the probit analysis and the tolerance-values were obtained with '$LD_{50}$ values for from 2nd-to 6th-instars/$LD_{50}$ values for first-instars.' The relative toxicities of the insecticides were 31so compared with the $LD_{50}$ values for the instars. The degree of tolerance was greatly increased as the larval instar advanced; the ranges of tolerance between the first-and 6th-instar larvae to the insecticides phoxim (Volaton), diazinon, chlorpyrifos (Dursban), carbofuran (Curaterr) and Mocap were 251.6, 126.6, 97.5, 44.3, and 18.7 times, respectively. The average relative toxicities of the insecticides for the instars indicated that the toxicity of phoxim was the greatest and following carbofuran, chlorpyrifos, Mocap and diazinon.

• Korean Journal of Head & Neck Oncology
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• v.27 no.1
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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.