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Differential routes of carboplatin administration influence lymphocyte apoptosis in retroperitoneal lymph nodes

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Tumor Biology

Abstract

We aimed to investigate carboplatin distribution in retroperitoneal lymph nodes and its effect on lymphocyte apoptosis following intravenous (IV), intra-arterial (IA), and retroperitoneal (RP) administration. Sixty-three healthy female canines were randomly assigned as IV, IA, or RP administration of carboplatin. At 0.5, 1, 2, 4, 8, 24, and 72 h after carboplatin treatment, retroperitoneal lymph nodes (n = 6 at each time point) were collected and high-performance liquid chromatography was employed to measure the carboplatin content. The differences in carboplatin pharmacokinetics of the three administration routes were compared. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was carried out to measure the lymphocyte apoptosis of the retroperitoneal lymphocytes. The peak concentration of carboplatin in plasma following IV administration was the highest among all approaches; as to the peak time, RP administration was longer than the other two administrations. Concentration for carboplatin in the retroperitoneal lymph node was highest following IA administration at early time points, but at higher time points, concentration was significantly higher following RP administration. Penetration of carboplatin into the retroperitoneal space was higher following RP administration. Following RP administration, the level of apoptotic lymphocytes in the retroperitoneal lymph nodes was significantly greater than either IV or IA. Following RP administration of carboplatin, the concentration, area under the curve of carboplatin and the number of apoptotic lymphocytes were significantly higher than those following IV and IA administration. This suggests that RP administration of carboplatin is beneficial for the treatment of retroperitoneal lymph node metastasis.

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Acknowledgments

This study was funded by research grants from the Technology Project of Guangdong Province (no. 2003C30313) and the Natural Science Foundation of Guangdong Province (no. 10451008901006144).

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, People’s Republic of China

    Yong-Wen Huang, Su Li & Ji-Hong Liu

  2. Department of Gynecology, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China

    Yong-Wen Huang & Ji-Hong Liu

  3. Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China

    Zheng Zeng

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  1. Yong-Wen Huang
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  2. Zheng Zeng
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  3. Su Li
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  4. Ji-Hong Liu
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Correspondence to Ji-Hong Liu.

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Huang, YW., Zeng, Z., Li, S. et al. Differential routes of carboplatin administration influence lymphocyte apoptosis in retroperitoneal lymph nodes. Tumor Biol. 33, 2053–2059 (2012). https://doi.org/10.1007/s13277-012-0464-6

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  • DOI: https://doi.org/10.1007/s13277-012-0464-6

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