• Clinical and Experimental Pediatrics
• /
• 제54권3호
• /
• pp.95-105
• /
• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

• 약학회지
• /
• 제55권5호
• /
• pp.391-397
• /
• 2011

KML001 reduced the proliferation of HCT116 cells in a concentration- and time-dependent manner without change of cell viability. Beclin-1 expression was significantly attenuated by KML001 (P<0.05), but no significant changes were observed in KML001-treated cells. The number of cells in G1 phase was increased 48 hr after KML001 treatment. Furthermore, a dramatic reduction in the frequency of beating and the number of embryoid bodies of the cells was noted after treatment. Taken together, KML001 suppresses the proliferation of HCT116 cells, which might be due to G1 phase arrest.

• 한국미생물·생명공학회지
• /
• 제42권2호
• /
• pp.152-161
• /
• 2014

The in vitro antimicrobial potential of the unexplored Moringa oleifera seed coat (SC) was evaluated against some Gram-positive and Gram-negative bacteria and yeast pathogens. Antimicrobial studies with various solvent extracts indicated ethyl acetate to be the best extractant, which was used for the rest of the antimicrobial studies as it tested neither toxic nor mutagenic. Gram-positive bacteria including a methicillin resistant Staphylococcus aureus (MRSA) strain were more susceptible with a minimum inhibitory concentration (MIC) range of 0.03-0.04 mg/ml. The antimicrobial pharmacodynamics of the extract exhibited both concentration-dependent and time-dependent killing. Most of the test organisms exhibited a short post antibiotic effect (PAE) except Enterococcus faecalis, Staphylococcus aureus, and Klebsiella pneumoniae 1, which exhibited longer PAEs. Amongst the major phytoconstituents established, flavonoids, diterpenes, triterpenes and cardiac glycosides exhibited inhibitory properties against most of the test organisms. The identified active phytochemicals of the M. oleifera seed coat exhibited antimicrobial potential against a wide range of medically important pathogens including the multidrug-resistant bugs. Hence, the M. oleifera seed coat, which is usually regarded as an agri-residue, could be a source of potential candidates for the development of drugs or drug leads of broad spectrum that includes multidrug-resistant bugs, which are one of the greatest concerns of the $21^{st}$ century.

• Toxicological Research
• /
• 제33권4호
• /
• pp.299-304
• /
• 2017

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

• Radiation Oncology Journal
• /
• 제28권1호
• /
• pp.23-31
• /
• 2010

목 적: 정상 장기의 부작용 확률(normal tissue complication probability, NTCP) 모델을 이용하여, 중심폐거리(central lung distance, CLD)와 최대심장거리(maximal heart distance)와 같은 이차원 방사선치료의 방사선학적 지표들과 삼차원 입체조형방사선치료의 부작용확률 사이의 관계를 평가해 보고자 하였다. 대상 및 방법: 2006년 11월부터 2007년 8월까지 서울아산병원에서 유방암으로 진단받고 수술 후 방사선치료를 시행 받은 110명을 무작위로 추출하여 분석하였다. 방사선치료는 2문 빗면 조사법, 3문 조사법, Reverse Hockey Stick법을 사용하였고, 유방 및 흉벽에는 5,040 cGy/28회, 쇄골 상부에는 4,500 cGy/25회로 조사하였고, 유방보존술을 시행한 경우에는 원발 병소에 1,000 cGy/4회의 추가치료를 하였다. 모든 환자에서 전산화단층촬영모의치료를 시행하였고, Eclipse Planning System을 사용하여 선량 계산을 시행 후 폐와 심장의 선량 부피 곡선(dose volume histogram, DVH)을 추출하였다. 추출된 DVH를 사용하여 modified Lymam model과 relative seriality model을 통해 NTCP를 계산하고 분석하였다. 결 과: 전체 환자의 방사선 폐렴과 심장 사망의 NTCP 값은 각각 0.5%, 0.7%로 낮은 수치를 보였다. 방사선 폐렴의 NTCP는 2문 조사법과 3문 조사법에 비해 Reverse Hockey Stick 법에서 높았다(0%, 0%, 3.1%, p<0.001). 방사선 폐렴의 NTCP 값은 중심폐거리가 커질수록 증가하였고, 심장 사망의 NTCP는 최대심장거리가 커질수록 증가하였다($R^2=0.808$). 결 론: 이차원 방사선치료의 방사선학적 지표들과 삼차원 입체조형방사선치료의 NTCP 값 사이에는 밀접한 관계가 있다. 이러한 연관성을 통해 과거의 부작용학률에 대한 자료들을 이차원 방사선치료의 방사선학적 지표들을 이용하여 NTCP 모델의 관점에서 재분석하는데 유용할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7171-7177
• /
• 2013

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

• 동의생리병리학회지
• /
• 제30권3호
• /
• pp.164-176
• /
• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

• 대한임상독성학회지
• /
• 제13권2호
• /
• pp.71-77
• /
• 2015

Purpose: Acute endosulfan poisoning is rare but causes significant morbidity and mortality. The aim of our study is to describe complications and features of seizure and determine factors associated with mortality in acute endosulfan poisoning. Methods: Twenty-eight adult patients with acute endosulfan poisoning admitted to our emergency department during a 15-year period were studied retrospectively. The clinical features of seizure, use of antiepileptic drugs during seizure, and hospital courses were evaluated. Clinical factors between survived group and non-survived group were compared for identification of factors associated with mortality. Results: Of the 28 patients with endosulfan poisoning, 4 patients (14.3%) died and 15 (53.6%) patients developed generalized tonic-clonic seizure. Thirteen patients (46.4%) and 5 patients (17.9%) progressed to status epilepticus (SE) and refractory status epilepticus (RSE), respectively. SE and RSE were associated with mortality. Almost all significant complications including shock, acute renal failure, hepatic toxicity, rhabdomyolysis, and cardiac injury developed in SE and RSE patients. Conclusion: SE and RSE were important contributors to death in endosulfan poisoning. Emergency physicians treating endosulfan poisoning should make an effort not to progress seizure following endosulfan poisoning to SE and RSE using a rapid and aggressive antiepileptic drug.

• BMB Reports
• /
• 제53권8호
• /
• pp.437-441
• /
• 2020

In accordance with requirements of the ICH S7B safety pharmacology guidelines, numerous next-generation cardiotoxicity studies using human stem cell-derived cardiomyocytes (CMs) are being conducted globally. Although several stem cell-derived CMs are being developed for commercialization, there is insufficient research to verify if these CMs can replace animal experiments. In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 μM isoproterenol, 5 μM doxorubicin, and 50 μM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have identified the advantages of hESC-CMs, which can distinguish between species variability, over electrophysiological analysis of ion channels against cardiac damage. Our findings demonstrate the possibility and advantage of high-efficiency hESC-CMs as next-generation cardiotoxicity assessment.

• 대한한방내과학회지
• /
• 제37권3호
• /
• pp.467-483
• /
• 2016

Objective: This study was performed to investigate the effect of IUS (Inulsan, an extract of Artemisiae capillaris (茵蔯), Curcumae longae (鬱金), and Crataegi fructus (山査)) on anti-hyperlipidemia, anti-oxidation, and anti-inflammation.Method: We administered water extracts of Artemisiae capillaris, Curcumae longae, and Crataegi fructus for three weeks to db/db mice (C57BL/Ks), animal models induced with type 2 diabetes mellitus. Mice were divided into three groups: normal (C57BL/6J mice group), control group (db/db mice without administration of IUS) and IUS group (db/db mice treated with IUS). Then we measured total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in the serum after the oral administration of IUS.Results: 1. IUS did not show any cytotoxicity in RAW 264.7 cells. 2. IUS decreased AST, ALP, and creatinine levelsand did not show any liver or renal toxicity in the db/db mice. 3. IUS increased DPPH and ABTS radical scavenging activity and decreased ROS production in RAW 264.7 cells. 4. IUS significantly decreased IL-1β, IL-6, and TNF-α production in RAW 264.7 cells. 5. IUS increased HDL cholesterol and significantly decreased total cholesterol and triglyceride in db/db mice. 6. IUS significantly decreased the atherogenic index and cardiac risk factor. 7. In contrast with the control group, fat infiltration in the liver and aorta decreased in IUS treated mice. The cell nucleus was located in the central area in H&E staining of liver. And endomembranes also were more thinner than the control group in H&E staining of aorta.Conclusions: These results suggest that IUS might be effective in the prevention and treatment of dyslipidemia.