Corvò R, Giaretti W, Margarino G, Danova M, Vitale V
Istituto Nazionale per la Ricerca sul Cancro, Genova.
Radiol Med. 1991 Jul-Aug;82(1-2):147-52.
Cell kinetics in 22 human epidermoid head and neck tumors were studied in vivo using bromodeoxyuridine (BUrD). Patients were infused with 250 mg/m2 of intravenous BUrD in a variety of sites (oral cavity, pharynx, larynx and lip) four/five hours prior to biopsy. BUrD incorporating cells were detected by flow-cytometry using anti-BUrD monoclonal antibodies. Ploidy (DNA index) labelling index (LI%), duration of S-phase (Ts) and potential doubling time (Tpot) could be measured within 12-24 hours from sampling in 77%, 72%, 63 and 63% of cases, respectively. Six failures (few viable cells in biopsy specimen and difficulties in BUrD cell analysis and DNA staining) were recorded. Labelling index values in this study ranged from 2.2% to 28% with a median value of 11%. The median total LI% of diploid tumor (n = 7) was 5% compared to 13% in aneuploid tumors (n = 7). Ts measurement ranged from 6.5 hours to 12 hours, median value being 10.5 hours (euploid tumors: 6.5, aneuploid 12). The calculated potential doubling time ranged from 2.6 to 15 days and the median Tpot was shorter at 5.0 days (euploid tumors: 7 days, aneuploid 4 days). 70% of the tumors had potential doubling time of 5 days or less. Potential doubling time did not correlate with ploidy and tumor or neck nodes status while shorter Tpots were observed in moderate or poorly differentiated tumors. Our data strongly suggest BUrD technique as a useful tool for studying the proliferative behavior of human tumors: the pre-treatment knowledge of individualized potential doubling times for the tumors scheduled for irradiation could help the radiotherapist to choose the more effective fractionation regimen (i.e.: accelerated fractionation for tumors with Tpot less than or equal to 6 days and standard fractionation for tumors with higher values.
利用溴脱氧尿苷（BUrD）在体内研究了22例人类头颈部表皮样肿瘤的细胞动力学。在活检前四/五个小时，通过多种部位（口腔、咽、喉和唇）给患者静脉输注250mg/m²的BUrD。使用抗BUrD单克隆抗体通过流式细胞术检测掺入BUrD的细胞。在采样后的12 - 24小时内，分别在77%、72%、63%和63%的病例中可以测量倍性（DNA指数）、标记指数（LI%）、S期持续时间（Ts）和潜在倍增时间（Tpot）。记录了6例失败情况（活检标本中活细胞很少以及在BUrD细胞分析和DNA染色方面存在困难）。本研究中的标记指数值范围为2.2%至28%，中位数为11%。二倍体肿瘤（n = 7）的总LI%中位数为5%，而在非整倍体肿瘤（n = 7）中为13%。Ts测量范围为6.5小时至12小时，中位数为10.5小时（整倍体肿瘤：6.5小时，非整倍体12小时）。计算出的潜在倍增时间范围为2.6至15天，Tpot中位数较短，为5.0天（整倍体肿瘤：7天，非整倍体4天）。70%的肿瘤潜在倍增时间为5天或更短。潜在倍增时间与倍性、肿瘤或颈部淋巴结状态无关，而在中度或低分化肿瘤中观察到较短的Tpot。我们的数据强烈表明BUrD技术是研究人类肿瘤增殖行为的有用工具：对于计划进行放疗的肿瘤，预先了解其个体化潜在倍增时间可以帮助放射治疗师选择更有效的分割方案（即：Tpot小于或等于6天的肿瘤采用加速分割，Tpot值较高的肿瘤采用标准分割）。
