Tumor growth and its chemotherapeutic regimens manifest myelosuppression, which is one of the possible causes underlying the limited success of immunotherapeutic anticancer strategies. Hence, approaches are being designed to develop safer therapeutic regimens that may have minimal damaging action on the process of myelopoiesis. 3-Bromopyruvate (3-BP) is a highly potent antimetabolic agent displaying a broad spectrum antineoplastic activity. However, 3-BP has not been investigated for its effect on the process of myelopoiesis in a tumor-bearing host. Hence, in this investigation, we studied the myelopoietic effect of in vivo administration of 3-BP to a murine host bearing a progressively growing ascitic thymoma designated as Dalton's lymphoma (DL). 3-BP administration to the DL-bearing mice resulted in a myelopotentiating action, reflected by an elevated count of bone marrow cells (BMC) accompanied by augmented proliferative ability and a declined induction of apoptosis. The BMC of 3-BP-administered mice displayed enhanced responsiveness to macrophage colony-stimulating factor for colony-forming ability of myeloid lineage along with an enhanced differentiation of F4/80+ bone marrow-derived macrophages (BMDM). BMDM differentiated from the BMC of 3-BP-administered DL-bearing mice showed an augmented response to lipopolysaccharide and interferon-γ for activation, displaying an augmented tumor cytotoxicity, expression of cytokines, reactive oxygen species, nitric oxide, CD11c, TLR-4, and HSP70. These features are indicative of the differentiation of M1 subtype of macrophages. Thus, this study demonstrates the myelopotentiating action of 3-BP, indicating its hematopoietic safety and potential for reinforcing the differentiation of macrophages in a tumor-bearing host.

中文翻译：

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Antimetabolic代理人3-Bromopyruvate在具有渐进性腹水性胸腺瘤的小鼠宿主中发挥骨髓增生作用。

肿瘤生长及其化学疗法表现出骨髓抑制，这是免疫治疗抗癌策略成功有限的可能原因之一。因此，正在设计方法来开发更安全的治疗方案，该方案可能对骨髓生成过程具有最小的破坏作用。3-溴丙酮酸（3-BP）是一种高效的抗代谢药，具有广谱抗肿瘤活性。然而，尚未研究3-BP对荷瘤宿主骨髓生成过程的影响。因此，在这项研究中，我们研究了将3-BP体内施用给携带着逐渐增多的腹水性胸腺瘤（称为道尔顿淋巴瘤（DL））的鼠宿主的骨髓生成作用。对带有DL的小鼠进行3-BP给药可产生骨髓增势作用，骨髓细胞（BMC）计数增加，伴随着增殖能力增强和凋亡诱导降低而反映出来。给予3-BP的小鼠的BMC表现出对巨噬细胞集落刺激因子的响应，增强了对髓系谱系集落形成能力的响应，同时增强了F4 / 80 +骨髓衍生巨噬细胞（BMDM）的分化。BMDM与3 BP给药的DL小鼠的BMC区别开来，对脂多糖和干扰素γ的激活反应增强，显示出增强的肿瘤细胞毒性，细胞因子表达，活性氧，一氧化氮，CD11c，TLR-4和HSP70。这些特征指示了巨噬细胞M1亚型的分化。因此，本研究证明了3-BP的骨髓增势作用，