Heterogeneity of tumor oxygenation: Relationship to tumor necrosis, tumor size, and metastasis
Heterogeneity of tumor oxygenation: Relationship to tumor necrosis, tumor size, and metastasis
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DOI：
10.1016/s0360-3016(98)00323-x
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发表时间：
1998-11-01
影响因子：
7
通讯作者：
Hill, RP
中科院分区：
文献类型：
--
作者：
De Jaeger, K;Merlo, FM;Hill, RP
目的：对移植的啮齿动物 KHT-C 和 SCC-VII 肿瘤中的氧合测量表明，正如在人类肿瘤中观察到的那样，肿瘤与肿瘤之间存在显着的异质性。这一发现表明，肿瘤之间氧合作用的异质性可能与肿瘤生长相关的因素有关，而不是与内在的遗传差异有关。在本研究中，我们检查了单个 KHT-C 肿瘤的氧合测量是否与肿瘤坏死或肿瘤大小有关，以及肿瘤缺氧程度是否会引起更多转移。方法：肿瘤在 C3H 小鼠的腓肠肌中生长，并使用 Eppendorf 极谱氧探针以规定尺寸（约 0.35 g、1.0 g 和 2.0 g）测量肿瘤氧合。通过检查用于氧测量的肿瘤的组织学切片来评估坏死。当肿瘤大小达到约 2 g 时，通过对处死小鼠的宏观肺结节进行计数来评估转移情况。结果：随着肿瘤变大，单个 KHT-C 肿瘤中的肿瘤氧合变得更差，坏死变得更广泛，但在 0.3-0.4 g 大小时，氧合和坏死程度之间没有关系。一般来说，在 0.3-8.4 g 大小时测量肿瘤 pO(2) 可预测肿瘤在大小约为 1 g 的同一肿瘤中，pO(2) 较高，但当肿瘤达到约 2 g 大小时，它们都处于严重缺氧状态。有趋势表明，KHT-C 肿瘤中肺肉眼可见转移与缺氧程度之间存在相关性，但这并不具有统计学意义。结论：结果表明，KHT-C 肿瘤中观察到的氧合异质性并不能用各个肿瘤中不同程度的坏死来解释，增加的缺氧程度与肺转移之间缺乏相关性。 KHT-C 肿瘤中转移的形成和缺氧水平的增加与人类肿瘤报道的结果不一致。 (C) 1998 爱思唯尔科学公司。
Purpose: Measurements of oxygenation in the transplanted rodent KHT-C and SCC-VII tumors demonstrate significant heterogeneity from tumor to tumor as is observed in human tumors. This finding suggests that heterogeneity in oxygenation between tumors is likely related to factors associated with tumor growth rather than to intrinsic genetic differences. In this study we examined whether measurements of the oxygenation of individual KHT-C tumors were related to necrosis in the tumors or to tumor size and whether the more hypoxic tumors gave rise to more metastases.Methods: Tumors were grown in the gastrocnemius muscle of C3H mice and tumor oxygenation was measured at defined sizes (approx, 0.35 g, 1.0 g, and 2.0 g) using an Eppendorf polarographic oxygen probe. Necrosis was assessed by examining histological sections curt from tumors used for the oxygen measurements. Metastasis was assessed by counting macroscopic lung nodules in mice sacrificed when their tumors reached a size of approximately 2 g.Results: Tumor oxygenation in individual KHT-C tumors became poorer and necrosis became more extensive as the tumors grew larger but, at a size of 0.3-0.4 g, there was no relationship between oxygenation and extent of necrosis, In general, measurements of tumor pO(2) at a size of 0.3-8.4 g were predictive of tumor pO(2) in the same tumor at a size of about 1 g, but by the time the tumors reached a size of about 2 g they were all very hypoxic, There was a trend suggesting a relationship between macroscopic metastases in the lung and degree of hypoxia in the KHT-C tumors but this was not statistically significant.Conclusion: The results indicate that the heterogeneity of oxygenation seen in KHT-C tumors is not explained by different degrees of necrosis in the individual tumors, The lack of a correlation between increased metastasis formation and increased levels of hypoxia in the KHT-C tumors is not consistent with results reported for human tumors. (C) 1998 Elsevier Science Inc.