Kotelnikov V M, Coon JS I V, Haleem A, Taylor S I V, Hutchinson J, Panje W, Caldarelli D D, Griem K, Preisler H D
Rush Cancer Institute, Department of Pathology, Department of Otolaryngology, and Department of Radiation Oncology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833, USA.
Clin Cancer Res. 1995 May;1(5):527-37.
We measured the tumor cell proliferative rate in 26 patients with head and neck cancer, 22 of which were squamous cell carcinomas (SCCs). Patients received sequential infusions of iododeoxyuridine and bromodeoxyuridine, after which the tumor was biopsied and studied. The percentage of labeled cells [labeling index (LI)] in well-differentiated SCCs was 20.4 +/- 2.7% (mean +/- SE) and 23.8 +/- 2.1% in moderately differentiated SCCs (P = 0.135). The LIs of two poorly differentiated SCCs were 39.4 and 55.9%. The LI was 2.5% in a high-grade lymphoepithelioma and 24.8% in a malignant lymphoma. In one well-differentiated and one poorly differentiated mucoepidermoid tumor, the LIs were 3.0% and 29.1%, respectively. S-phase duration time measurements ranged from 5.1-21.5 h (12.8 +/- 1.5). The calculated potential doubling times ranged from 18.8-84.5 h (47.3 +/- 6.7). The duration of G2 was between 90 and 180 min. To track the fate of labeled cells, in four patients a repeat biopsy was obtained 7-14 days after the iododeoxyuridine/bromodeoxyuridine infusion. These patients did not receive treatment between the biopsies. Due to the dilution of the label, most labeled cells in the second biopsy demonstrated a "fragmented" pattern resulting from repeated cell divisions. In two patients, however, 25% of cells in the second biopsy had undiluted label, suggesting that these cells had not divided after incorporating iododeoxyuridine/bromodeoxyuridine. On Day 7 labeled cells migrated to keratinized parts of tumors and to necrotic foci. Thus, the arrest of cell cycle transition, tumor cell differentiation, and cell death may be major routes of tumor cell loss from the proliferative compartment. This may explain the difference between very short potential doubling times and the actual rate of tumor growth.
我们测量了26例头颈癌患者的肿瘤细胞增殖率，其中22例为鳞状细胞癌（SCC）。患者接受碘脱氧尿苷和溴脱氧尿苷的序贯输注，之后对肿瘤进行活检并研究。高分化SCC中标记细胞的百分比[标记指数（LI）]为20.4±2.7%（均值±标准误），中分化SCC为23.8±2.1%（P = 0.135）。两例低分化SCC的LI分别为39.4%和55.9%。一例高分化淋巴上皮瘤的LI为2.5%，一例恶性淋巴瘤为24.8%。在一例高分化和一例低分化黏液表皮样瘤中，LI分别为�.0%和29.1%。S期持续时间测量范围为5.1 - 21.5小时（12.8±1.5）。计算出的潜在倍增时间范围为18.8 - 84.5小时（47.3±6.7）。G2期持续时间在90至180分钟之间。为追踪标记细胞的命运，4例患者在碘脱氧尿苷/溴脱氧尿苷输注后7 - 14天进行了重复活检。这些患者在两次活检之间未接受治疗。由于标记的稀释，第二次活检中大多数标记细胞呈现出因细胞反复分裂导致的“碎片化”模式。然而，在两例患者中，第二次活检中25%的细胞具有未稀释的标记，表明这些细胞在掺入碘脱氧尿苷/溴脱氧尿苷后未分裂。在第7天，标记细胞迁移至肿瘤的角化部位和坏死灶。因此，细胞周期转换的停滞、肿瘤细胞分化和细胞死亡可能是增殖区室中肿瘤细胞丢失的主要途径。这可能解释了非常短的潜在倍增时间与肿瘤实际生长速率之间的差异。
