• Radiation Oncology Journal
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• 제21권3호
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• pp.192-198
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• 2003

목적: 급성 골수성 백혈병에서 자가 조혈모세포 이식은 무병생존율에 도움을 주며 1차 관해된 급성 골수성 백혈병에서 자가 조혈모세포 이식은 점차 늘어나고 있는 추세이다. 본 연구는 1차 관해된 급성 골수성 백혈병에서 자가 조혈모세포 이식을 위한 전처치 요법으로 cytarabine, melphalan과 전신 방사선치료를 시행하여 그 효과를 알아보고자 하였다. 대상 및 방법: 1995년 1월부터 1999년 12월까지 급성 골수성 백혈병으로 1차 관해 후 자가 조혈모세포 이식을 받은 29명을 대상으로 하였다. 환자의 중앙연령은 33세(16~47세)이었다. 자가 조혈모세포 이식을 위한 전처치 요법은 cytarabine ($3.0\;gm/m^2$, 3일), melphalan ($100\;gm/m^2$, 1일)과 전신 방사선치료를 시행하였다. 전신 방사선치료는 6MV 선형가속기를 이용하여 200 cGy를 1일 2회씩 5회 분할 조사하여 총 조사선량은 1000 cGy이었다. 결과: 추적 관찰기간은 3~58개월이었으며 중앙값은 40개월이었다. 전체 환자의 4년 무병생존율은 69.0%이었으며 중앙생존기간은 41.5개월이었다. 4년 재발률은 27.6%이었다. 무병생존율과 재발률에 영향을 미치는 인자 분석에서는 FAB 분류만이 유의한 예후인자로 분석되었다($M_3$군 vs. $M_3$를 제외한 군; p=0.048, p=0.043). 대 상 환자 중 9명에서 사망하였으며 치료와 관련된 사망은 1명이었고 8명은 재발로 사망하였다. 결론: 1차 관해된 급성 골수성 백혈병에서 자가 조혈모세포 이식을 위한 melphalan, cytarabine과 전신 방사선치료는 비교적 효과적인 전처치 요법이었다.

• Archives of Pharmacal Research
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• 제8권3호
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• pp.159-168
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• 1985

In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumor agent, cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior of in vitro distribution, drug release behaior, and degradation of albumin microspheres in animal liver tissue homogenate and proteolytic enzyme were investigated. The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was affected by dispersion forces during emulsification and albumin concentration. Distribution of albumin mirospheres after intravenous administration in rabbit was achieved immediately. In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin micropheres was not changed. Albumin microsphere matrix was degraded by the rabbit liver tissue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.

• Archives of Pharmacal Research
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• 제12권2호
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• pp.88-93
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• 1989

In order to obtain some informations about the effect of molecular weight on the release rate of drug from drug carrier, two types of poly-L-glutamic acid (PLGA)-cytarabine (ara-C) conjugates, PLGA-ara-C:I and PLGA-ara-C:II, were synthesized using two types of PLGA having different average molecular weight, 43,000 and 77,800, respectively. The PLGA-ara-C conjugates were synthesized by mixed anhydride method and found to be covalently linked. Both types of conjugates charged negatively at biological pH. The pH-dependent release rate of ara-C was observed in both cases, and the release rate was accelerated in basic, acidic conditions (the k values were 0.015 $day^{-1}$ at pH 7.0, 0.024 $day^{-1}$ at pH 5.0, and 0.059 $day^{-1}$ at pH 9.0 in the case of PLGA-ara-C:I) and in the presence of pretense. The time required for the release of 16.5% of ara-C from PLGA-ara-C:I were 8 hr and 144 hr in the presence and absence of protease, respectively. Although both types of conjugates showed similar drug substitution ratio, they showed different release rates. Between the two types of conjugates, PLGA-ara-C:II showed the faster release rate (0.030 vs 0.042 $day^{-1}$ in pH 7.4 phosphate buffer solution at $37^{\circ}C$) and the smaller activation energy for the release of drug (12.5 vs 7.7 Kcal/mol) than PLGA-ara-C:I. The characteristic effect of molecular weight on the release rates of PLGA-ara-C conjugates suggests that the drug release rate might be effectively controlled over a prolonged period of time by the combined use of the different types of PLGA-ara-C conjugates having different molecular weights.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.129-133
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• 1993

Temperature sensitive liposomes(TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drug, Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature $(T_c)$ of TSL was dependent on the lipid compositions of TSL ADM broadened thermogram of TSL but Ara-C did not. However, $T_c$ of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near $T_c$ and observed at $39-41^\circ{C}$ for DPPC (Dipalmitoylphosphatidylcholine) only, $52-54^\circ{C}$ for DPPC and DSPC (1:1), respectively. Effect of human serum alburmin (HAA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below $T_c$. However, ADM release from TSL was increased at the near and above $T_c$. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near TEX>$4^\circ{C}$. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at TEX>$4^\circ{C}$ was not changed, the TSL was considered to be stable for at least 1 week at TEX>$4^\circ{C}$. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1169-1181
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• 2018

Background/Aims: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited. Methods: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. Results: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. $6.1{\times}10^6/kg$, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ${\geq}5.0{\times}10^6/kg$) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < $2.0{\times}10^6/kg$) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). Conclusions: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.167-167
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• 1994

Thioglycerol과 Glycerol을 출발물질로 1번 탄소(C) 위치의 산소(O),또는 황(S)에 octadecyl기로 alkylation한 후, 2번 탄소(C)위치 산소(O)를 palmitoyl기로acetylation시켜 만든 thioether lipid 및 ether lipid유도체를 인산화시킨 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL-PTBA-P)와 rac-1-O-octadecyl-2-O-palmitoylglycerol-3-phosphate (DL-PBA-P)등을 합성하였다. 이들 thioether lipid 및 ether lipid유도체는 그 자체로도 in vitro와 in vivo에서anti-neoplastic property를 가지고 있는데, 이들 중간체를 핵산 화합물로써 역시 강한 항암 작용에도 불구하고 독성등 부작용이 문제가 되고있는 Ara-C (일명 Cytarabine)의 인산화물인 ara-CMP morpholidate와 conjugation시켜 최종물질로서 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 중 ara-CDP-DL-PTBA가 본 과제와 관련하여 항암제로서 최종 개발하고자하는 주요 물질인 Cytoros이다.

• 한국임상수의학회지
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• 제31권3호
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• pp.226-232
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• 2014

8개월령의 단모종 집고양이가 감소된 식욕과 활력 저하로 내원하였다. 진단을 위한 영상 검사에서 종격동의 종괴와 종격동 림프절의 비대 소견을 확인할 수 있었다. 이어서 진행한 세침흡인술 검사로, 악성 림프구를 다수 확인할 수 있었으며, 이 고양이는 다발성 림프종 (병기 V-b)로 진단되었다. 치료는 COP 프로토콜을 사용하였으며, 완전 완화를 확인할 수 있었지만, 항암 치료를 시작한 후 314일 째 재발과 함께 중추신경계로 전이된 소견을 확인할 수 있었다. 구조화학 요법을 실시하여, 단기적으로는 임상증상의 큰 개선을 확인할 수 있었지만, 부분완화만이 관찰되었으며, 처음 내원 부터 약 383일 정도 생존하였다. 부검과 조직병리학적 검사를 통해, 다발성의 T 세포 림프종으로 확인하였으며, 뇌에서도 병변을 확인할 수 있었다.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.248-255
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• 2005

To understand the response of cancer cells to anticancer drugs at the gene expression level, we examined the gene expression changes in response to five anticancer drugs, 5-fluorouracil, cytarabine, cisplatin, paclitaxel, and cytochalasin D in NCI-H460 human lung cancer cells. Of the five drugs, 5-fluorouracil had the most distinctive gene expression signature. By clustering genes whose expression changed significantly, we identified three clusters with unique gene expression patterns. The first cluster reflected the up-regulation of gene expression by cisplatin, and included genes involved in cell death and DNA repair. The second cluster pointed to a general reduction of gene expression by most of the anticancer drugs tested. A number of genes in this cluster are involved in signal transduction that is important for communication between cells and reception of extracellular signals. The last cluster represented reduced gene expression in response to 5-fluorouracil, the genes involved being implicated in DNA metabolism, the cell cycle, and RNA processing. Since the gene expression signature of 5-fluorouracil was unique, we investigated it in more detail. Significance analysis of microarray data (SAM) identified 808 genes whose expression was significantly altered by 5-fluorouracil. Among the up-regulated genes, those affecting apoptosis were the most noteworthy. The down-regulated genes were mainly associated with transcription-and translation-related processes which are known targets of 5-fluorouracil. These results suggest that the gene expression signature of an anticancer drug is closely related to its physiological action and the response of caner cells.

• BLOOD RESEARCH
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• 제53권4호
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• pp.288-293
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• 2018

Background Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. Methods Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. Results The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. Conclusion Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.