• Title/Summary/Keyword: cell toxicity

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Effect of $Cd^{2+}$ on the Oocyte Maturation and Developmental Stages of Brown Frog Embryo, Rana dybowskii in vitro ($Cd^{2+}$이 북방산개구리의 난자성숙과 배아발달에 미치는 영향)

  • Ko Sun-Kun
    • Korean Journal of Environment and Ecology
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    • v.20 no.3
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    • pp.345-351
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    • 2006
  • This study investigates the toxic effects of $Cd^{2+}$on frog (Rana dybowskii) by the determination of oocyte maturation and development of embryo exposure to different concentrations of the toxicant. The results show that $Cd^{2+}$ concentration of 0.1ppm suppressed the maturation of the oocytes. To examine the reversibility of the inhibitory effects, the oocytes were exposed to the $Cd^{2+}$ only for 3 hours, and then transferred to plain medium and cultured further for 17 hours. The oocytes were recovered from the toxic effect of the $Cd^{2+}$ when they were exposed to 1ppm, but not to 2.5ppm of the $Cd^{2+}$. The development of 2 cell embryos to 32 cell was completely suppressed at 0.1ppm and the longer the embryos were exposed to the $Cd^{2+}$, the more damage appeared to the embryos and the cytolysis of the 32 cell was induced by $Cd^{2+}$ at 0.1ppm. On the other hand, the embryos of blastula stage were cultured 96 hours in presence of the $Cd^{2+}$ at various concentrations and were examined. The rates of mortality and malformed larvae were investigated by probit analysis. From the results of LC$_{50}$ of 0.1ppm and EC$_{50}$ of 0.08ppm, Tl of 5.0 was derived, which indicates $Cd^{2+}$ is to be considered a teratogenic compound. Such specific malformations occurred in 14.3% as spine deformations at the 0.05ppm, in 75.0% as tail deformations at the 0.1ppm, in 66.7% as abdominal deformations at the 0.01ppm and in 26.0% as profound deformations at the 0.1ppm of $Cd^{2+}$ concentration which living embryos were exposed to. $Cd^{2+}$ suppressed growth to head-tail length at 0.1ppm. In conclusion, The study results reveal that $Cd^{2+}$ must be considered highly toxic effect to oocyte maturation and embryonic development.

Characteristics of mushroom Phellinus baumii extracts with enzyme pretreatment (효소 전처리에 의한 상황버섯 β-glucan 추출물의 특성)

  • Son, Eun Ji;Ryu, Eun-Ah;Lee, Sang-Han;Kim, Young-Chan;Hwang, In-Wook;Chung, Shin-Kyo
    • Journal of Applied Biological Chemistry
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    • v.61 no.1
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    • pp.101-108
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    • 2018
  • This study was conducted to establish optimized ${\beta}-glucan$ extraction method through enzymatic hydrolysis from Phellinus baumii and investigate ${\beta}-glucan$ contents and physicochemical properties. The optimal condition was obtained with the enzyme concentration of 0.66% (v/v), reaction time of 6.08 h ($R^2=0.9245$) and the ${\beta}-glucan$ contents from the Phellinus baumii extracts under the optimized condition was 1.9594 g/100 g. ${\beta}-Glucan$ yield (0.76-16.40%) of enzyme beta-glucan extract (EBE) was three fold higher than that of non-enzyme beta-glucan extract (NEBE). ${\beta}-Glucan$ purity (11.15-59.05%) of non-enzyme beta-glucan (NEB) and that of enzyme beta-glucan (EB) were higher than that of NEBE and that of EBE. ${\beta}-Glucan$ purity of EB (59.05%) and ${\beta}-glucan$ contents of EB (3.38 g/100 g) showed higher than those of others. Total sugar contents (0.61-1.17 mg/mL) showed that NEB and EB were higher than that of NEBE and EBE, EB had the highest total sugar content as 1.17 mg/mL, respectively. Protein contents (0.44-11.73 mg/mL) of NEBE and that of EBE were higher than that of NEB, that of EB. In FT-IR spectrum, the band at $890cm^{-1}$ of microcapsule was attributed to a ${\beta}-1,3-glucan$. The toxicities of ${\beta}-glucan$ from Phellinus baumii in both melanoma cell lines was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoli um bromide assay and ${\beta}-glucan$ from Phellinus baumii has no toxicity until $30{\mu}g/mL$. The effects of ${\beta}-glucan$ from Phellinus baumii on inhibition of cancer cell proliferation were detected by using a wound healing assay. The effect of NEB and EB were higher than NEBE and EBE, especially $30{\mu}g/mL$ of EB had the highest in both melanoma cell lines.

Clinical Study of Topotecan as Second-Line Treatment in Small Cell Lung Cancer (소세포폐암의 2차요법으로서의 Topotecan의 치료효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.3
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    • pp.230-240
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    • 2002
  • Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

Concurrent Docetaxel/Cisplatin and Thoracic Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (국소 진행성 비소세포 폐암에서 Docetaxel Cisplatin을 사용한 화학-방사선 동시치료의 효과)

  • Jang, Tae Won;Park, Jung Pil;Kim, Hee Kyoo;Ok, Chul Ho;Jeung, Tae Sig;Jung, Maan Hong
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.257-264
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    • 2004
  • Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer (재발된 소세포폐암환자에서 이차 약제로 사용되는 Belotecan (CKD-602)의 임상적 효용성)

  • Ban, Hee-Jung;Oh, In-Jae;Kim, Kyu-Sik;Ju, Jin-Yung;Kwon, Yong-Soo;Kim, Yu-Il;Lim, Sung-Chul;Kim, Young-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.2
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    • pp.93-97
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    • 2009
  • Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

Responses and Toxicities of Risk-adapted Chemotherapy in Pediatric Intracranial Germ Cell Tumors (소아 두개 내 생식 세포종에서 위험군에 따른 화학요법의 치료 반응 및 독성)

  • You, Dong Kil;Lee, Soo Hyun;Yoo, Keon Hee;Sung, Ki Woong;Lim, Do Hoon;Shin, Hyung Jin;Koo, Hong Hoe
    • Clinical and Experimental Pediatrics
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    • v.48 no.2
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    • pp.186-190
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    • 2005
  • Purpose : The purpose of this study was to evaluate the responses and toxicities of risk-adapted chemotherapy in pediatric intracranial germ cell tumors(IC-GCT). Methods : Fourteen patients who were diagnosed as IC-GCT from October 2002 to December 2003 received chemotherapy as an initial treatment modality. The low risk(LR) group was defined as follows : Pure germinoma and normal AFP level. Beta-hCG level 50 mIU/mL or less. The others belonged to the high risk(HR) group. Chemotherapy was composed of cisplatin, cyclophosphamide, etoposide and vincristine. Double doses of cisplatin and cyclophosphamide was used in HR patients. Results : Pathologic confirmation was done in all but one. Median age at diagnosis was 11.6 yr (1.2-18.7 yr), and nine patients belonged to the HR group. Tumor markers were normalized after chemotherapy in all patients whose tumor markers had been elevated. Four LR patients(80 percent) and seven HR patients(77.8 percent) showed complete response(CR) at the end of chemotherapy. An additional two of the three patients with partial response(PR) achieved CR after radiation therapy (RT), and the remaining one relapsed before RT. Four LR and all HR patients experienced infectious episodes that required hospitalization. Four of the nine HR patients(44.4 percent) suffered from tinnitus, three of whom developed sensorineural hearing loss. All but one are surviving, event-free, with a median follow-up of 13.9 mo(8.1-22.3 mo). Conclusion : Risk-adapted cisplatin-based chemotherapy was effective even in HR patients, but regimen modification seems to be necessary to avoid an unacceptably high toxicity rate.

Retrospective Analysis of Chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer (제한병기 소세포암 환자의 항암화학방사선요법에 대한 후향적 분석)

  • Lee, Jong-Hoon;Kim, Sung-Hwan;Kim, Su-Zy;Lee, Joo-Hwan;Kim, Hoon-Kyo;Shim, Byoung-Yong
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.133-139
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    • 2009
  • Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.

Inhibitory Effects of Asparagus cochinchinensis in LPS-Stimulated BV-2 Microglial Cells through Regulation of Neuroinflammatory Mediators, the MAP Kinase Pathway, and the Cell Cycle (Lipopolysaccharide로 자극된 BV-2 미세교세포에서 신경염증 매개체, MAP kinase경로, 세포주기의 조절에 의한 천문동(Asparagus cochinchinensis)의 저해효과)

  • Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
    • Journal of Life Science
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    • v.30 no.4
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    • pp.331-342
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

Phase II Trial of Irinotecan plus Cisplatin Combination as First Line Therapy for Patients with Small cell Lung Cancer (소세포폐암 환자에서 1차 항암 치료제로서 Irinotecan 과 Cisplatin 병합요법에 관한 2상 연구)

  • Jeong, Hye Cheol;Lee, Sang Yeub;Kim, Jung Ha;Ha, Eun Sil;Jung, Jin Yong;Lee, Kyung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Lee, Sung Yong;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.1
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    • pp.57-64
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    • 2006
  • Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

Protective Effects of Enzymatic Oyster Hydrolysate on Acetaminophen-induced HepG-2 Cell Damage (아세트아미노펜 유도 HepG-2 세포주 손상에 대한 굴 효소 가수분해물의 보호 효과)

  • Park, Si-Hyang;Moon, Sung-Sil;Xie, Cheng-Liang;Choung, Se-Young;Choi, Yeung-Joon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.8
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    • pp.1166-1173
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    • 2014
  • This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.