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Prophylactic broad spectrum antibiotics as a new anti-myeloma therapy

机译:预防性广谱抗生素作为一种新的抗骨髓瘤疗法

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Multiple myeloma is a common, yet incurable, haematological neoplasm. The reciprocal communication between malignant plasma cells, other cell types, and the extracellular matrix in the bone marrow micro-eco system is mediated by cell-cell and cell-matrix adhesion, as well as the production of different soluble factors, and is crucial for tumour growth and drug resistance. Inflammation and pro-inflammatory cytokines contribute to the clonal expansion of neoplastic plasmacytes. This extremely complex pathogenesis of multiple myeloma gives us the opportunity to promote numerous novel drugs and approaches based on the paradigm of targeted therapy. Immune dysfunction is a hallmark of multiple myeloma. Intrinsic and therapy-related immunosuppression leads to an increased risk of recurrent infection, the major cause of mortality. However, little data is available regarding the possible influence of infection on the biology and progression of multiple myeloma. Some authors have shown that pathogenic microorganisms can activate tool-like receptors on myeloma cells, as well as the robust production of pro-inflammatory cytokines; together these factors can contribute to myeloma growth, survival, and progression. Therefore, we proposed a simple, inexpensive, and new approach for anti-myeloma therapy that, to the best of our knowledge, is the first one concerning the prophylactic, long-term use of broad-spectrum antibiotics during the course of disease regardless of the chosen concomitant regimens. Prophylactic treatment with antibiotics should suppress the pro-inflammatory milieu produced during recurrent bacterial infections and prevent the activation of tool-like receptors on tumour cells, which are important factors responsible for tumour growth and survival in patients with multiple myeloma.
机译:多发性骨髓瘤是一种常见但无法治愈的血液肿瘤。恶性浆细胞,其他细胞类型与骨髓微生态系统中的细胞外基质之间的相互通讯是由细胞与细胞和细胞基质的粘附以及不同可溶性因子的产生介导的,这对于肿瘤生长和耐药性。炎症和促炎细胞因子有助于肿瘤性浆细胞的克隆扩增。多发性骨髓瘤的这种极其复杂的发病机制使我们有机会基于靶向治疗的范式推广众多新药和新方法。免疫功能障碍是多发性骨髓瘤的标志。与治疗相关的内在和免疫抑制作用导致反复感染的风险增加,这是造成死亡的主要原因。然而,关于感染对多发性骨髓瘤的生物学和进展的可能影响的数据很少。一些作者表明,病原微生物可以激活骨髓瘤细胞上的工具样受体,并能强烈产生促炎性细胞因子。这些因素一起可以促进骨髓瘤的生长,存活和发展。因此,我们提出了一种简单,廉价且新的抗骨髓瘤治疗方法,据我们所知,它是第一个涉及在疾病过程中预防,长期使用广谱抗生素的方法,无论选择的伴随方案。抗生素的预防性治疗应抑制细菌反复感染期间产生的促炎环境,并防止肿瘤细胞上工具样受体的活化,这是导致多发性骨髓瘤患者肿瘤生长和存活的重要因素。

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