In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment
In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment
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DOI：
10.1016/s0360-3016(00)01470-x
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发表时间：
2001-02-01
影响因子：
7
通讯作者：
Lambin, P
中科院分区：
文献类型：
--
作者：
Landuyt, W;Ahmed, B;Lambin, P
目的：通过抗血管生成或血管靶向干扰肿瘤血管，可以间接抑制肿瘤生长。使用微管蛋白受损药物对实体瘤进行血管靶向似乎是一种有前景且选择性的新型治疗方法。我们的目的是评估使用考布他汀 A-4 磷酸盐 (combreAp) 与电离辐射或抗血管生成的血管靶向组合的潜在（基于假设的）益处。方法和材料：将横纹肌肉瘤肿瘤块皮下（s.c.）植入同基因成年 WAG/Rij 大鼠的较低等级区域，肿瘤发出不同的大小并分层为不同的治疗组：小（1-3） cm(3))、中号 (3.1-7 cm(3)) 和大号 (7.1-14 cm(3))，CombreAp 腹膜内注射； TNP-470 皮下注射在颈部区域。在戊巴比妥麻醉下对肿瘤进行局部单剂量（8 Gy）照射，总是在单次combreAp（25 mg/kg）注射前1天进行。 TNP-470治疗（1周内3次30mg/kg）在两次（两次之间间隔8天）combreAp施用后第1天开始。通过生长延迟测定评估肿瘤反应，并计算肿瘤生长变化的统计显着性。结果：大肿瘤对单独给予combreAp治疗的反应比小肿瘤更好，证实了我们之前使用该肿瘤模型的数据。结合放疗和combreAp 也导致了肿瘤大小依赖性的生长延迟。对于中小肿瘤体积，与仅照射相比，联合治疗后测量到类似的反应。然而，大肿瘤在联合治疗中显示出生长延迟的强烈（至少累加）增加；两个治疗组之间的肿瘤生长差异非常显着（p < 0.0001），当TNP-470与combreAp联合使用时，无论肿瘤大小如何，在应用的方案中都没有出现生长延迟的显着延长。结论：目前的数据显示在治疗时大尺寸（7-14 cm(3)）横纹肌肉瘤中combreAp与放疗的联合治疗具有显着优势。在较小的肿瘤中没有观察到肿瘤反应的这种益处，这似乎是因为放射本身非常有效。当 TNP-470 时，没有观察到任何肿瘤大小的生长延迟显着增加，特别是在肿瘤测量中显示出其自身的功效
Purpose: Interference with the tumor blood vessels through anti-angiogenesis or vascular targeting can indirectly suppress tumor growth. Vascular targeting of solid tumors, using tubulin-compromising agents, seems a promising and selective novel treatment. We aimed to evaluate the potential (hypothesis-based) benefit from combinations of vascular targeting using combretastatin A-4 phosphate (combreAp) with either ionizing radiation or anti-angiogenesis.Methods and Materials: Rhabdomyosarcoma tumor pieces were inplanted subcutaneously (s.c.) in the lower Rank region of syngeneic adult WAG/Rij rats, Tumors were groan until different sizes and stratified for the various treatment groups: small (1-3 cm(3)), medium (3.1-7 cm(3)), and large (7.1-14 cm(3)), CombreAp was injected i.p.; injections of TNP-470 were s.c. in the neck area. Localized single-dose (8 Gy) irradiations of tumors were done under Nembutal anesthesia, always 1 day before a single combreAp (25 mg/kg) injection. The TNP-470 treatment (3 times 30 mg/kg in 1 week) started I day after a double (8 days interval between both) combreAp administration. Tumor responses were evaluated by the growth delay assay, and statistical significance of tumor growth change was computed.Results: Large tumors responded better to combreAp treatment given alone than did the smaller ones, confirming our previous data with this tumor model. Combining irradiation with combreAp also resulted in a tumor size-dependent growth delay. With small and medium tumor volumes, a similar response was measured after the combination treatment when compared with irradiation only. Large tumors, however, showed a strong (at Least additive) increase of the growth delay with the combined therapy; the difference in tumor growth between the two treatment groups was very significant (p < 0.0001),When TNP-470 was combined with combreAp, no significant lengthening of the growth delay, irrespective of the tumor size, was present with the applied schedule.Conclusion: The current data show a significant advantage in the combination of combreAp with irradiation in rhabdomyosarcomas having a large size (7-14 cm(3)) at treatment. Such a benefit in tumor response was not observed with the smaller tumors, seemingly because irradiation as such was very effective. No significant gain in growth delay for any tumor size was observed when TNP-470, showing efficacy on its own specifically with tumors measuring