• Radiation Oncology Journal
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• v.38 no.2
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• pp.109-118
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• 2020

Purpose: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. Methods: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at d_max and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). Results: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. Conclusion: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. NCT04175821).

• Journal of Life Science
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• v.33 no.10
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• pp.842-850
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• 2023

Pyrrolnitrin, pyrrolomycin, and pyoluteorin are functional halogenated phenylpyrrole derivatives (HPDs) derived from microorganisms with diverse antimicrobial activities. Pyrrolnitrin is a secondary metabolite produced from L-tryptophan through four-step reactions in Pseudomonas fluorescens, Burkholderia cepacia, Serratia plymuthica, etc. It is currently used for the treatment of superficial dermatophytic fungal infections, has high antagonistic activities against soil-borne and foliar fungal infections, and has many industrial applications. Since pyrrolnitrin is easily decomposed by light, it is difficult to widely use it outdoors. As an alternative, fludioxonil, a synthetically produced non-systemic surface fungicide that is structurally similar and has excellent light stability, has been commercialized for seed and foliar treatment of plants. However, due to its high toxicity to aquatic organisms and adverse effects in human cell lines, many countries have established maximum residue levels and strictly control its levels. Pyrrolomycin and pyoluteorin, which have antibiotic/antibiofilm activity against Gram-positive bacteria and high anti-oomycete activity against the plant pathogen Pythium ultimum, respectively, were isolated and identified from microorganisms. This review summarizes the biosynthesis and production of natural pyrrolnitrin derived from bacteria and the characteristics of synthetic fludioxonil and other natural phenylpyrrole derivatives among the HPDs. We expect that a plethora of highly effective, novel HPDs that are safe for humans and environments will be developed through the generation of an HPD library by microbial biosynthesis and chemical synthesis.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.155-168
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• 2002

Purpose; Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-system involvement and renal damage is a major cause of morbidity and mortality in children. Renal involvement is more common and severe in children than in adults. Therefore, renal biopsy plays a crucial role in planning effective therapy. In this study, we investigated the clinical and pathological findings of lupus nephritis in children to aid clinical care of the disease. Methods: The clinical and pathological data of 40 patients who were diagnosed as SLE with renal involvement in Shinchon Severance Hospital from Jan. 1990 to Sep. 2002 were analyzed retrospectively. Results: The ratio of male to female patients was 1:3 and the median age at diagnosis was 12.1(2-18) years old. FANA(95.0%), anti-ds DNA antibody(87.5%), malar rash(80.0%) were the most common findings among the classification criteria by ARA. Microscopic hematuria with proteinuria(75.0%), nephrotic syndrome(55.0%), and microscopic hematuria alone(15.0%) were the most common renal presentations in the respective order at diagnosis. There were 27 cases with WHO class IV lupus nephritis confirmed by renal biopsy and 3 cases with pathological changes of WHO class type. Different treatment modalities were carried out : prednisolone only in 5 cases, prednisol-one+azat-hioprine in 9 cases, prednisolone+azathioprine+intravenous cyclophosphamide in 14 cases, prednisolone+cyclosporine A+intravenous cyclophosphamide in 12 cases, plasma exchange in 9 cases and intravenous gamma-globulin in 2 cases. The average follow-up period was $51.8{\pm}40.5$ months. During $51.8{\pm}40.5$ months. During follow-up, 4 patients expired. The risk factors associated with mortality were male, WHO class IV and acute renal failure at diagnosis. Conclusion: Renal involvement was noted in 63.5% of childhood SLE, and 67.5% of renal lesion was WHO class IV lupus nephritis which is known to be associated with a poor prognosis. Therefore aggressive treatment employing immunosuppressant during the early stages of disease could be helpful in improving long-term prognosis. But careful attention should be given to optimize the treatment due to unique problems associated with growth, psychosocial development and gonadal toxicity, especially in children.

• The Korean Journal of Pesticide Science
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• v.17 no.4
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• pp.363-370
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• 2013

Susceptibility of each developmental stage of Phthorimaea operculella (Lepidoptera: Gelechiidae) were investigated using 16 insecticides which are available in the market in Korea. For the eggs and pupae, only spinosad showed a 71.1% inhibition rate for egg hatchability and a 66.7% inhibition rate for emergence. For the 3rd instar larvae, the feeding toxicities were over 90% for fenitrothion ($LC_{50}$ 336.6 ppm), esfenvalerate ($LC_{50}$ 8.6 ppm), ethofenprox ($LC_{50}$ 35.7 ppm), and emamectin benzoate ($LC_{50}$ 0.05 ppm). Furthermore, the contact toxicities were over 90% for esfenvalerate ($LC_{50}$ 0.87 ppm), ethofenprox ($LC_{50}$ 16.5 ppm), emamectin benzoate ($LC_{50}$ 0.53 ppm), and spinosad ($LC_{50}$ 2.48 ppm) at the recommended concentrations. Deltamethrin and spinosad yielded 100% mortality for adult P. operculella 48 h after treatment. The adult female fecundity was inhibited by deltamethrin, esfenvalerate, emamectin benzoate, spinosad and dinotefuran, which were significantly different from the control. The adult longevities (7.3-8.3 days) were reduced by approximately 1-2 days compared with the control (9.3 day). The emamectin benzoate maintained 100% insecticidal activity 14 days after treatment and ethofenprox maintained over 90% activity 7 days after treatment.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.34-63
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• 2003

Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

• Korean Journal of Food Science and Technology
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• v.35 no.5
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• pp.980-987
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• 2003

In this report, we investigated the detoxication effects of Saururus chinenis, Geranium nepalense, Lonicera japonica, Cassia obtusifolia, Glycyrrhiza uralensis, or their mixtures by employing acute toxicity tests for nicotine and dioxin. When fatal doses $(LD_{100}\;=\;42\;mg/kg)$ of nicotine were injected into the abdominal cavities of ICR mice, those treated with OHEM showed delayed paralysis, half the duration of hyperactivity, and a 73 % survival rate. The results revealed the strong detoxicating effects of the mixtures. We also measured the amount of the degradation product of nicotine and cotinine in humans. Consumption of OHEM promoted (he more specific) the metabolic pathways of nicotine, increasing continine excretion by 1.5 times. As a result the amount of cotinine in urine was reduced to less than 5% after treatment with OHEM. In order to test the toxicity of dioxin, we used TcnN(SD)BR rats exposed to TCDD. While TCDD treatment reduced the blood levels of hemoglobin and platelet, OHEM consumption relieved these effects and, furthermore, helped to recover the number of platelet to the normal level (p<0.05). Moreover, neutrophils (%) and monocytes (%), which were reduced by the injection of TCDD, recovered to normal levels upon treatment with OHEM. The amount albumin reduced by TCDD (p<0.05) normalized, while the activities of GOT and GTP increased by TCDD were reduced. Increases in total cholesterol and neutral fatty acids induced by TCDD were also reduced by OHEM injection (p<0.05). In the kidney, TCDD-induced rises in creatinine were suppressed by OHEM treatment, while decreases in iron levels from TCDD were raised to normal. The treatment of TCDD had more toxic effects in the blood and pancreas than on the liver, kidney and heart. On the other hand, the detoxication of OHEM had significant effects on the liver and pancreas. The normalization by OHEM of various clinical abnormalities induced by TCDD demonstrates the detoxicating effect of OHEM that ameliorates systemic metabolism not properly functioning.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.451-474
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• 1993

Lidocaline if frequently administered as a component of an anesthetic : for local or regional nerve blocks, to mitigate the autonomic response to laryngoscopy and tracheal intubation, to suppress the cough reflex, and for antiarrythmic therapy. Diazepam dectease the potential central nervous system (CNS) toxicity of local anesthetic agents but may modify the sitmulant action of lidocaine in addition to their own cardiovascular depressant. The potential cardiovascular toxicity of local anesthetics may be enhanced by the concomitant administration of diazepam. This study was designed to investigate the effects of lidocaine dose and pretreated diazepam to cardiovascular system and plasma concentration of lidocaine. Lidocaine in 100 mcg/kg/min, 200 mcg/kg/min, and 300 mcg/kg/min was given by sequential infusion to dogs anesthetized with halothane-nitrous oxide (Group I). And in group II, after diazepam pretreatment, lidocaine was infused by same way when lidocaine was administered in 100 mcg/kg/min, the low plasma levels ($3.97{\pm}0.22-4.48{\pm}0.36$ mcg/ml) caused a little reduction in cardiovascular hemodynamics. As administered in 200 mcg/kg/min, 300 mcg/kg/min, the higher plasma levels ($7.50{\pm}0.66-11.83{\pm}0.59$ mcg/ml) reduced mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), left ventricular stroke work index (LVSWI), and right ventricular stroke work index (PVSWI) and increased pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), systemic vascular resistance index (SVRI), but was associated with little changes of heart rate (HR), mean pulmonary artery pressure (MPAP), and pulmonary vascular resistance index (PVRI). When lidocaine with pretreated diazepam was administered in 100 mcg/kg/min, the low plasma level, the lower level than when only lidocaine administered, reduced MAP, but was not changed other cardiovascular hemodynamics. While lidocaine was infused in 200 mcg/kg/min, 300 mcg/kg/min in dogs pretreated diazepam, the higher plasma level ($7.64{\pm}0.79-13.79{\pm}0.82$ mcg/ml) was maintained and was associated with reduced CI, SI, LVSWI and incresed PAWP, CVP, SVRI but was a little changes of HR, MPAP, PVRI. After $CaCl_2$ administeration, CI, SI, SVRI, LVSWI was recovered but PAWP, CVP was rather increased than recovered. The foregoing results demonstrate that pretreated diazepam imposes no additional burden on cardiovascular system when a infusion of large dose of lidocaine is given to dogs anesthetized with halothanenitrous oxide. But caution may be advised if the addition of lidocaine is indicated in subjects who have impared autonomic nervous system and who are in hypercarbic, hypoxic, or acidotic states.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.122-127
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• 2003

Purpose: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn't duplicate the result. the purpose of this study was to evaluate the relative efficacy & toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. Materials and Methods: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/$m^{2}$ IV for $1\∼5 days$), adriamycin (20 mg/$m^{2}$ IV for $1\∼5 days$) and cisplatin (20 mg/$m^{2}$ IV for $1\∼5 days$) and Twenty-eight patients receieved ELF chemotherapy : etoposide (100 mg/$m^{2}$ IV for $1\∼3 days$), leucovorin (20 mg/$m^{2}$ IV for $1\∼5 days$) and 5-FU (500 mg/$m^{2}$ IV for $1\∼5 days$). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient..ELF means 4.1 cycles per patient Results: Total respones rates were $5.4\%$ in the ELF group and $3.6\%$ in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value<0.05), and themedian overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis & hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: $27.6\%$ in ELF vs $54\%$ in EAP-II; Leukopenia: $8.5\%$ in ELF vs $19\%$ in EAP-II; nausea & vomiting: $45.9\%$ in ELF vs $67.8\%$ in EAP-II. Conclusion: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer (J Korean Gastric Cancer Assoc 2003;3:122-127)

• Radiation Oncology Journal
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• v.19 no.4
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• pp.359-368
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• 2001

Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materiaals : From 1991 Jan. through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated with induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of all patients was 70 months. Resulst : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was $67.3\%$. Complete remission rate was $80\%$ (20/25). Sixty-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a $67.3\%$ overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.