• Clinical and Experimental Pediatrics
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• 제46권3호
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• pp.242-249
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• 2003

목 적 : 항암치료 중 anthracycline을 사용한 환아들에 대한 후향적 조사를 통해 anthracycline의 축적량과 anthracycline 심독성과의 관계를 알고자 했고 심독성 환아들에 대한 추적 조사를 통해 anthracycline 심독성 환아의 예후를 알고자 하였다. 방 법 : 1995년 1월부터 2000년 12월까지 서울대학교병원 소아과에서 anthracycline을 포함한 항암치료를 시작한 환아를 대상으로 과거 anthracycline 축적량과 심장 초음파 검사 소견, 심독성 발생 유무 등을 조사하였다. 심독성은 좌심실 수축분율이 26% 이하로 감소한 경우로 정하였고 이들을 다시 좌심실 수축분율이 20%가 넘는 경증 심독성과 20% 미만인 중증 심독성으로 분류하였다. Anthracycline 심독성이 발생한 환아들에게 운동 능력과 심장 초음파, 심전도 검사, 흉부 방사선 촬영 등의 추적 검사를 시행하였다. 결 과 : 총 조사대상 환아는 154명이었다. 이 중에서 40명(26.0%)의 anthracycline 심독성이 발생하였으며 경증 심독성이 27명(17.5%), 중증 심독성이 13명(8.4%)이었다. 심독성의 발생률은 anthracycline의 축적량이 증가함에 따라 서서히 증가하다가 축적량이 $300mg/m^2$ 이상부터 갑자기 지수적으로 증가하는 양상을 보였다. 심독성 환아 40명 중 12명이 추적조사 이전에 사망하였고 생존한 환아 중 23명에 대해 추적검사를 시행하였다. Anthracycline의 사용을 중단한 후 평균 $3.6{\pm}1.8$년의 추적검사 결과 심독성 환아들의 좌심실 수축분율은 유의하게 증가하였다(P<0.01). 흉부 방사선 촬영이나 심전도 검사는 심독성의 진단을 위해 민감도와 특이도가 매우 낮은 검사였다. 결 론 : 일반적으로 anthracycline 심독성 환아의 추적검사로 시행하는 심전도 검사나 흉부 방사선 촬영은 심독성의 추적 조사에 도움이 되지 않는다. 심독성 환아들은 일단 생존하여 항암치료를 마치고 약 2-5년 정도 경과하면 심부전 증상이나 심장초음파 검사상 대부분 호전을 보인다.

• Clinical and Experimental Pediatrics
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• 제56권3호
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• pp.130-134
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• 2013

Purpose: Anthracyclines have been utilized in the treatment of children with acute lymphoblastic leukemia (ALL). Recent studies have shown that anthracyclines may induce toxicity in the vascular endothelium. This study was performed using brachial artery reactivity (BAR) to evaluate vascular endothelial function in ALL patients who were treated with anthracycline chemotherapy. Methods: We included 21 children with ALL who received anthracycline chemotherapy and 20 healthy children. The cumulative dose of anthracyclines in the ALL patients was $142.5{\pm}18.2/m^2$. The last anthracycline dose was administered to the patients 2 to 85 months prior to their examination using BAR. The diameter of the brachial artery was measured in both groups using echocardiography, and BAR was calculated as the percentage change in the arterial diameter after release of the cuff relative to the baseline vessel diameter. Results: In the anthracycline-treated group, BAR was observed to be $3.4%{\pm}3.9%$, which was significantly lower than that observed in the control group ($12.1%{\pm}8.0%$, P<0.05). The time elapsed after the last anthracycline treatment and the age at the time of treatment did not affect the change in BAR (P =0.06 and P =0.13, respectively). Conclusion: These results provided evidence that treatment of ALL patients with anthracycline results in endothelial dysfunction. A larger cohort study and a longer follow-up period will be required to clarify the relationship between endothelial dysfunction resulting from anthracycline treatment for childhood ALL and occurrence of cardiovascular diseases later in life.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5655-5661
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• 2015

Purpose: To assess the role of two adjuvant chemotherapy regimens, anthracycline-based and CMF on disease free survival and overall survival breast cancer patients by meta-analysis approach in Eastern Mediterranean and Asian countries to determine which is more effective and evaluate the appropriateness and efficiency of two different proposed statistical models. Materials and Methods: Survival curves were digitized and the survival proportions and times were extracted and modeled to appropriate covariates by two multivariate mixed effects models. Studies which reported disease free survival and overall survival curves for anthracycline-based or CMF as adjuvant chemotherapy that were published in English in the Eastern Mediterranean region and Asia were included in this systematic review. The two transformations of survival probabilities (Ln (-Ln(S)) and Ln(S/ (1-S))) as dependent variables were modeled by a multivariate mixed model to same covariates in order to have precise estimations with high power and appropriate interpretation of covariate effects. The analysis was carried out with SAS Proc MIXED and STATA software. Results: A total of 32 studies from the published literature were analysed, covering 4,092 patients who received anthracycline-based and 2,501 treated with CMF for the disease free survival and in order to analyze the overall survival, 13 studies reported the overall survival curves in which 2,050 cases were treated with anthracycline-based and 1,282 with CMF regimens. Conclusions: The findings illustrated that the model with dependent variable Ln (-Ln(S)) had more precise estimations of the covariate effects and showed significant difference between the effects of two adjuvant chemotherapy regimens. Anthracycline-based treatment gave better disease free survival and overall survival. As an IPD meta-analysis in the Italy the results of Angelo et al in 2011 also confirmed that anthracycline-based regimens were more effective for survival of breast cancer patients. The findings of Zare et al 2012 on disease free survival curves in Asia also provided similar evidence.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2013-2017
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• 2013

Background: To compare the effects of two adjuvant chemotherapy regimens, anthracycline-based and cyclophosphamide, methotrexate, fluorourical (CMF) on disease free survival for breast cancer patients in the Eastern Mediterranean region and Asia. Methods: In a systematic review with a multivariate mixed model meta-analysis, the reported survival proportion at multiple time points in different studies were combined. Our data sources were studies linking the two chemotherapy regimens on an adjuvant basis with disease free survival published in English and Persian in the Eastern Mediterranean region and Asia. All survival curves were generated with Graphdigitizer software. Results: 14 retrospective cohort studies were located from electronic databases. We analyzed data for 1,086 patients who received anthracycline-based treatment and 1,109 given CMF treatment. For determination of survival proportions and time we usesb the transformation Ln (-Ln(S)) and Ln (time) to make precise estimations and then fit the model. All analyses were carried out with STATA software. Conclusions: Our findings showed a significant efficacy of anthracycline-based adjuvant therapy regarding disease free survival of breast cancer. As a limitation in this meta-analysis we used studies with different types of anthracycline-based regimens.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.172-172
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• 1994

1960년대 이후 광범위한 항암제로서 그 임상효과가 탁월한 물질로 알려진 Anthracycline계 항생물질이 화학구조상 B환의 Hydroquinone형에 의한 생체내 산화환원 반응으로 이해 심근 독성에 영향을 준다고 알려져 있다. 이에 본 연구실에서는 Anthracycline의 Aqlycone 부분 12번 탄소의 전자친화력을 증가시키는 11번 탄소의 Hydroxy group이 제거되고 9번 탄소의 Hydroxy group을 Amine으로 대체함과 동시에 4번 탄소의 Methoxy group이 제거된 보다 독성이 적을 것이라 생각되는 Anthracycline의 새로운 Aglycone 유도체를 Design 하여 전합성 하였다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.111-111
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• 1993

Anthracycline의 합성에 있어서 aglycone 뿐만 아니고 sugar도 대단히 중요한 역할을 한다. Anthracycline에 이용되는 sugar인 daunosamine의 전합성의 확립을 통하여 daunosamine의 anlogue을 합성할 목적으로 daunosamine의 전합성을 검토하고 있다. Methyl D-mannopyranoside을 원료로 하여 0-methylation, PhCH(OMe)$_2$ 에 의한 OH의 보호, n-BuLi을 이용한 위치선택적 deblocking, oxime생성, 이어서 Vitride를 이용한 환원으로 daunosamine 합성에 있어서 중요한 중간체인 methyl-3-amino-4,6-benzylidene-2,3-dideoxy-$\alpha$-D-hexopyranoside을 합성하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2301-2305
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• 2016

Background: The early detection of anthracycline- induced cardiotoxicity is very important since it might be useful in prevention of cardiac decompensation. This study was designed with the intent of assessing the usefulness of cardiac troponin T (cTnT) and NT- Pro BNP estimation in early prediction of anthracycline induced cardiotoxicity. Materials and Methods: In this prospective study histologically proven breast cancer patients who were scheduled to receive anthracycline containing combination chemotherapy as a part of multimodality treatment were enrolled. Baseline cardiac evaluation was performed by echocardiography (ECHO) and biomarkers like cardiac troponin T (cTnT) and N terminal- pro brain natriuretic peptide (NT- Pro BNP). All patients underwent cTnT and NT- Pro BNP estimation within 24 hours of each cycle of chemotherapy and were followed up after 6 months of initiation of chemotherapy. Any changes in follow up ECHO were compared to ECHO at baseline and cTnT and NT- Pro BNP levels after each cycle of anthracycline-based chemotherapy. Results: Initial data were obtained for 33 patients. Mean change in left ventricular diastolic diameter (LVDD) within 6 months was $0.154{\pm}0.433cms$ (p value=0.049). Seven out of 33 patients had an increase in biomarker cTnT levels (p value=0.5). A significant change in baseline and follow up LVDD was observed in patients with raised cTnT levels (p value=0.026) whereas no change was seen in ejection fraction (EF) and left atrial diameters (LAD) within 6 months of chemotherapy. NT- Pro BNP levels increased in significant number of patients (p value ${\leq}0.0001$) but no statistically significant change was observed in the ECHO parameters within 6 months. Conclusions: Functional monitoring is a poorly effective method in early estimation of anthracycline induced cardiac dysfunction. Estimation of biomarkers after chemotherapy may allow stratification of patients in various risk groups, thereby opening window for interventional strategies in order to prevent permanent damage to the myocardium.

• Bulletin of the Korean Chemical Society
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• 제27권9호
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• pp.1359-1363
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• 2006

Novel anthracycline analogues 2-9 as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium lactate, and stearic acid, respectively. Compounds 3-5 and 7-9 were prepared by the reaction of either daunomycin (1a) or doxorubicin (1b) with L-lactic and stearic acids in the presence of EDCI/PP reagents.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.226-235
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• 1993

DA-125, a new anthracycline antitumor antibiotic, was administered to Sprague-Dawley rats intravenously for 4 weeks to investigate the repeated dose toxicity Focal alopecia was noted in three female rats receiving 1.0mg/kg/day. In rats receiving 1.0 mg/kg/day, weight gain decreased in both sexes after first or second week. Hematological examination revealed lower counts of total leukocyte and increased numbers of platelet after second week. At terminal necropsy, atrophy of thymus and spleen was observed. Lymphocytic depletion of thymus and atrophy of white pulp in spleen were observed microscopically. A decrease in the number of hematopoietic cells in the bone marrow and degeneration of germinal epithelia in testes were also observed. These treatment-related effects were mainly confined to rats receiving 1.0 mg/kg/day. And toxic effects with microscopic changes were not observed in rats receiving 0.2 mg/kg/day or 0.04 mg/kg/day.

• 약학회지
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• 제38권6호
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• pp.749-755
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• 1994

An interspecific fusant strain, Streptomyces MS1 was obtained by protoplast fusion between S. peucetius subsp. caesius and S. platensis. We studied on the fermentation characteristics of the fusant strain. The fermentation products of the fusant MS1 was identical with S. peucetius, but its production of anthracycline was more stable than S. peucetius under various fermentation conditions in regard to acidogenesis of fermentation broth. The optimal medium composition for anthracycline production by fusant MS1 as follows: sucrose 2.0%, glucose 1.0%, soytone 0.7%, $CaCO_3$ 0.2%, $KH_2PO_4$ 0.013%, casamino acids 0.01%, $K_2SO_4$ 0.025%, $MaCl_2\;6H_2O$ 1.024%, 5M $CaCl_2\;5H_2O$ 0.4%, 1N NaOH 0.7%, 20% L-proline 1.5%. In this condition, the productivity of anthracycline was $80{\sim}100\;{\mu}g/ml$.