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晚期肺癌患者骨髓培养物中的成纤维细胞集落形成单位以及肿瘤坏死因子和前列腺素E2水平。

Fibroblastic colony-forming units and levels of tumor necrosis factor and prostaglandin E2 in bone marrow cultures from patients with advanced lung carcinoma.

作者信息

Chasseing N A, Bordenave R H, Bullorsky E O, Diaz N B, Stemmelin G R, Rumi L S

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, Buenos Aires.

出版信息

Cancer. 1997 Nov 15;80(10):1914-9.

PMID:9366293
Abstract

BACKGROUND

Although alterations of the bone marrow (BM) fibroblast colony-forming cells are involved in the development of diverse hematologic disorders, these progenitors still have not been well characterized in patients with solid tumors.

METHODS

The incidence of fibroblast colony-forming units (CFU-F) was evaluated in the cultures of unseparated and fractionated light density BM mononuclear cells (MC) from 25 consecutive untreated lung carcinoma patients (LCP) and 16 normal controls (NC). Unseparated MC also were cultured in the presence of indomethacin (10[-6] M). Finally, the authors evaluated the spontaneous production of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) in culture conditioned mediums of unseparated MC by radioimmunoassay and enzyme-linked immunoadsorbent assay methodology, respectively.

RESULTS

A decreased number of CFU-F was observed in unseparated and fractionated (adherent and nonadherent) light density MC cultures from LCP compared with NC. When unseparated MC of LCP were treated with indomethacin, a slightly increase in the number of CFU-F was found. Adherent MC (stromal cells) achieved confluence only in 44% of LCP primary cultures compared with 100% of NC. Overproduction of PGE2 and TNF-alpha was found in the conditioned mediums of LCP compared with the mean values obtained in NC (P < 0.05 and P < 0.02, respectively).

CONCLUSIONS

The lack of confluence and suppression of CFU-F in BM of LCP may be related to the increase production of PGE2 and TNF-alpha. Future investigation will allow the determination of how these modifications influence tumor cell growth and will prove if more alterations of the hematopoietic microenvironment imply a worse prognosis.

摘要

背景

尽管骨髓(BM)成纤维细胞集落形成细胞的改变参与了多种血液系统疾病的发生发展,但在实体瘤患者中,这些祖细胞仍未得到很好的表征。

方法

评估了25例连续未经未经连续未治疗的肺癌患者(LCP)和16例正常对照(NC)的未分离及分级低密度BM单核细胞(MC)培养物中成纤维细胞集落形成单位(CFU-F)的发生率。未分离的MC也在吲哚美辛(10[-6] M)存在的情况下进行培养。最后,作者分别通过放射免疫测定法和酶联免疫吸附测定法评估了未分离MC培养条件培养基中前列腺素E2(PGE2)和肿瘤坏死因子-α(TNF-α)的自发产生情况。

结果

与NC相比,LCP未分离及分级(贴壁和非贴壁)低密度MC培养物中观察到CFU-F数量减少。当LCP的未分离MC用吲哚美辛处理时,发现CFU-F数量略有增加。与100%的NC相比,贴壁MC(基质细胞)仅在44%的LCP原代培养物中达到汇合。与NC获得的平均值相比,LCP的条件培养基中发现PGE2和TNF-α产生过多(分别为P < 0.05和P < 0.02)。

结论

LCP骨髓中CFU-F缺乏汇合和受到抑制可能与PGE2和TNF-α产生增加有关。未来的研究将确定这些改变如何影响肿瘤细胞生长,并将证明造血微环境的更多改变是否意味着更差的预后。

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