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激光光辐射疗法对HL-60、Daudi和U-937细胞系中克隆形成肿瘤细胞的清除作用:对自体骨髓净化的意义。

Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging.

作者信息

Gulliya K S, Pervaiz S

机构信息

Baylor Research Foundation, Baylor University Medical Center, Dallas, TX 75246.

出版信息

Blood. 1989 Mar;73(4):1059-65.

PMID:2920207
Abstract

Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin's lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray-irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested. These results may have therapeutic relevance in patients undergoing interferon treatment who require bone marrow transplantation, as the complete elimination of tumor cells by marrow-purging procedures may be hampered by this increased survival in the presence of interferon.

摘要

在体外模型中测试了激光光辐射疗法消除非霍奇金淋巴瘤细胞的疗效。结果显示,在存在20微克/毫升部花青540(MC540)的情况下,当激光能量为31.2焦/平方厘米时,伯基特淋巴瘤(Daudi)细胞减少了超过5个对数。在激光能量剂量为93.6焦/平方厘米时,白血病(HL - 60)细胞也有类似的肿瘤细胞杀伤效果。然而,为了对组织细胞淋巴瘤(U - 937)细胞获得相同的杀伤效率,则需要更高剂量的MC540(25微克/毫升)。激光光辐射疗法后,克隆性肿瘤干细胞集落形成减少了超过5个对数。在每种细胞系的相同条件下,粒细胞 - 巨噬细胞集落形成单位(CFU - GM,45.9%、40%、17.5%)、粒细胞/红细胞/巨噬细胞/巨核细胞(GEMM,40.1%、20.1%、11.5%)、集落形成单位(CFU - C,16.2%、9.1%、1.8%)和红细胞爆式集落形成单位(BFU - E,33.4%、17.8%、3.9%)的存活百分比显著高于肿瘤细胞。将γ射线照射的正常骨髓细胞与肿瘤细胞以1:1和10:1的比例混合,并不干扰肿瘤细胞的消除。还研究了高度纯化的重组干扰素α(rIFN)对肿瘤细胞激光光辐射疗法的影响。在存在rIFN(30至3000单位/毫升)的情况下,观察到白血病细胞的活力从0%增加到1.5%,同时膜极化降低,这表明细胞膜流动性因rIFN而增加。然而,在更高剂量的rIFN(6000至12000单位/毫升)下未观察到这种现象。在所有测试的rIFN剂量下,淋巴瘤细胞的活力均未受影响。这些结果对于接受干扰素治疗且需要进行骨髓移植的患者可能具有治疗相关性,因为在干扰素存在的情况下,这种存活率的增加可能会阻碍通过骨髓净化程序完全消除肿瘤细胞。

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