Comte L, Lorgeot V, Volkov L, Roullet B, Tubiana N, Praloran V
Laboratoire d and apos;Hèmatologie Experimentale, Faculté de Médecine,Limoges, France.
Cancer Lett. 1997 Jan 15;112(1):1-4. doi: 10.1016/S0304-3835(96)04494-1.
The tetrapeptide AcSer-Asp-Lys-Pro (AcSDKP) is a physiological inhibitor of the proliferation of haematopoietic stem cells and progenitors. In Ara-C-treated mice, its plasmatic concentrations decrease while the CFU-S start cycling. Infusion of synthetic AcSDKP (Goralatide) at this time protects them from haematoxicity by blocking early cycling of CFU-S. Both in vitro and in vivo, this effect seems to be optimal in a narrow range of concentrations. Thus, a better knowledge of the kinetics of endogenous AcSDKP during cancer treatment could help to optimize the treatments with Goralatide. AcSDKP plasma levels have been measured by a specific EIA in 14 cancer patients during the two initial monthly 5 day courses of chemotherapy with 5-FU alone administered either by continuous infusions (six patients) or by 1 h daily infusions (eight patients). AcSDKP concentrations did not vary significantly during the first and the second course. Together with our previous results in AML patients treated with high doses chemotherapy (Ara-C and Anthracyclin), our present data suggest that the variations of endogenous AcSDKP in patients are dependent of the type, doses and schedule of chemotherapy.
四肽AcSer-Asp-Lys-Pro（AcSDKP）是造血干细胞和祖细胞增殖的生理抑制剂。在接受阿糖胞苷治疗的小鼠中，其血浆浓度降低，而脾集落形成单位（CFU-S）开始进入细胞周期。此时输注合成的AcSDKP（戈拉替德）可通过阻止CFU-S的早期细胞周期来保护它们免受血液毒性。在体外和体内，这种效应似乎在狭窄的浓度范围内最为显著。因此，更好地了解癌症治疗期间内源性AcSDKP的动力学有助于优化戈拉替德的治疗。在14例癌症患者接受最初两个每月为期5天的化疗疗程期间，通过特异性酶免疫分析（EIA）测量了AcSDKP的血浆水平，化疗仅使用5-氟尿嘧啶（5-FU），其中6例患者采用持续输注，8例患者采用每日1小时输注。在第一个疗程和第二个疗程期间，AcSDKP浓度没有显著变化。结合我们之前对接受高剂量化疗（阿糖胞苷和蒽环类药物）的急性髓系白血病（AML）患者的研究结果，我们目前的数据表明，患者体内内源性AcSDKP的变化取决于化疗的类型、剂量和疗程。
