Experimental study on the effect of pre-administered THP-ADM on the tissue levels of CDDP.

简介：在我们的临床研究中，THP-ADM、CDDP和PEP的新辅助化疗（TPP治疗）显示了头颈部癌的高原发疗效。预先植入的THP-ADM在TPP治疗中的作用尚未得到充分研究。本文通过实验研究了预先给予THP-ADM对CDDP组织水平的影响。将VX-2癌移植到日本白色兔的腿中，动脉内或静脉内用CDDP治疗0.5小时A组（A-0.5或IV-0.5）、IA-24或IV-24组（IA-48或IV-48组）、C组（C组）分别于给药后24小时、48小时给予顺铂。THP-ADM剂量为1 mg/kg，CDDP剂量为2 mg/kg。给药后30 min取血和组织，用火焰原子吸收法测定CDDP的含量，用高效液相色谱法测定THP-ADM及其代谢产物的含量。IA-0.5组中的肿瘤中[0.199 μ g/g] ...更多信息 与对照组（2.898 ± 0.01）相比，差异有统计学意义（P < 0.05）。（1.213 μ g/g）。IA-24组肿瘤中观察到的CDDP水平无显著差异（1.533 ± 0.001）。IA-48组（1.425 ± 0.001 μ g/g），IA-48组（1.973 ± 0.001 μ g/g），IA-48组（1.425 ± 0.001 μ g/g）。IA-24组淋巴结中CDDP水平显著高于C组（P<0.05）（3.391 ± 0.001）。1.991 μ g/g）比IA-0.5（1.357 μ g/g）高。IA-48组（2.903 ± 0.427 μ g/g）; 1.182 μ g/g）或C组（1.195 μ g/g）。[）0.818 μ g/g）。四组间血浆CDDP水平无显著差异。同样，在IV-0.5、IV-24和IV-48组中CDDP水平没有显著差异。讨论：实验表明，预先施用THP-ADM对组织中CDDP浓度有有益作用。这种效应可能解释TPP治疗的临床证据。THP-ADM和CDDP联合化疗的上述作用可能是化疗的生化调节作用之一。因此，这些发现初步支持TPP疗法是头颈癌的适当治疗的理论。少

INTRODUCTION : In our clinical study, neoadjuvant chemoterapy of THP-ADM,CDDP and PEP (TPP therapy) showed high primary effect on head and neck cancer. The roles of pre-admisintered THP-ADM in TPP therapy has not been investigated thoroughly enough. In this paper, the effects of pre-administered THP-ADM on the tissue levels of CDDP were studied experimentally.MATERIALS & METHODS : VX-2 carcinoma transplanted into the leg of Japanese white rabbits was treated intraarterially or intravenously with CDDP 0.5 hrs (group IA-0.5 or IV-0.5), 24 hrs (group IA-24 or IV-24) and 48 hrs (group IA-48 or IV-48) after administrating THP-ADM,or only CDDP without THP-ADM (group C). The dose of THP-ADM was 1 mg/kg, and CDDP 2 mg/kg, respectively. Blood and tissue were collected 30 minutes after the administration of CDDP.The level of CDDP was measured by the FAAS,and THP-ADM and their metabolites were analyzed by the HPLC.RESULTS : The CDDP level (0.815(]SY.+-。[)0.199mug/g) in the tumors in group IA-0.5 … More was significantly lower than in group C (2.898(]SY.+-。[)1.213mug/g). There was no marked difference in the CDDP levels observed in the tumors among group IA-24 (1.533(]SY.+-。[)1.973mug/g), group IA-48 (1.425(]SY.+-。[)1.243mug/g) or group C.The level of CDDP in the lymph node was observed to be significantly higher (p<0.05) in group IA-24 (3.391(]SY.+-。[)1.991mug/g) than in group IA-0.5 (1.357(]SY.+-。[)0.427mug/g), group IA-48 (2.903(]SY.+-。[)1.182mug/g) or group C (1.195(]SY.+-。[)0.818mug/g). There were no significant differences in the plasma CDDP levels among the four groups. Similarly, there were no significant differences in the CDDP levels among group IV-0.5, IV-24 and IV-48.DISCUSSION : Experimentally, pre-administered THP-ADM demonstrated the beneficial effects on CDDP consentration in the tissue. Potentially, this effect may explain the clinical evidence for TPP therapy. These effects of combined chemotherapy of THP-ADM and CDDP is suspected to be one type of the biochemical modulations. Therefore, these findings tentatively support the theory of TPP therapy that is an adequate treatment of the head and neck cancer. Less