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L-天冬酰胺酶对猫淋巴瘤血浆氨基酸谱和肿瘤负荷的影响。

Effects of L-asparaginase on plasma amino acid profiles and tumor burden in cats with lymphoma.

作者信息

LeBlanc A K, Cox S K, Kirk C A, Newman S J, Bartges J W, Legendre A M

机构信息

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, C247 Veterinary Teaching Hospital, 2407 River Drive, Knoxville, TN 37996-4544, USA.

出版信息

J Vet Intern Med. 2007 Jul-Aug;21(4):760-3. doi: 10.1892/0891-6640(2007)21[760:eolopa]2.0.co;2.

DOI:10.1892/0891-6640(2007)21[760:eolopa]2.0.co;2
PMID:17708396
Abstract

BACKGROUND

L-Asparaginase (Elspar(a)), is an Escherichia coli-derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown.

HYPOTHESES

L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats.

ANIMALS

Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment.

METHODS

Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response.

RESULTS

Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged.

CONCLUSIONS AND CLINICAL IMPORTANCE

L-asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%.

摘要

背景

左旋门冬酰胺酶(Elspar(a))是一种源自大肠杆菌的酶,它能使淋巴瘤细胞中的天冬酰胺耗竭,抑制蛋白质合成并导致细胞死亡。左旋门冬酰胺酶对猫淋巴瘤的单药反应率以及其对血浆氨基酸浓度的影响尚不清楚。

假设

左旋门冬酰胺酶能显著降低血浆中天冬酰胺浓度,且对未经治疗的猫淋巴瘤具有明显疗效。

动物

13只确诊为任何解剖部位淋巴瘤(LSA)的猫接受1剂400 IU/kg肌肉注射的左旋门冬酰胺酶进行初始LSA治疗。

方法

在左旋门冬酰胺酶治疗后0、2和7天采集血浆,检测氨、天冬酰胺、天冬氨酸、谷氨酰胺和谷氨酸的浓度。7天后对猫进行重新分期以评估肿瘤反应。

结果

8只猫为T细胞LSA,4只猫为B细胞LSA,1只猫的免疫表型未知。观察到2例完全缓解和2例部分缓解。4只猫病情稳定,5只猫病情进展。治疗后2天和7天,氨和天冬氨酸浓度较基线升高。治疗后2天天冬酰胺浓度较基线降低,但7天时未降低。与治疗后7天相比,治疗后2天谷氨酸浓度升高,但与基线相比未升高。谷氨酰胺浓度未变。

结论及临床意义

左旋门冬酰胺酶在治疗后2天内显著降低了天冬酰胺浓度,但这种效果在7天内消失。本研究中猫LSA对左旋门冬酰胺酶的明显总体反应率为30%。

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