Dralle H, Böcker W, Döhler K D, Schröder S, Haindl H, Geerlings H, Schwarzrock R, Pichlmayr R
Cancer Res. 1985 Mar;45(3):1239-45.
Tissue was taken from 16 patients with benign thyroid lesions (10 nontoxic nodular colloid goiter, two follicular adenoma, one autonomous adenoma, one iodine-induced thyrotoxicosis, 2 Graves' disease) and 18 patients with malignant thyroid tumors [seven papillary, five follicular, five undifferentiated (anaplastic), and one medullalry carcinoma] and was xenotransplanted into the flanks of 124 syngeneic female BALB/c-nu/nu mice 6 weeks of age. Subsequently, without any further treatment, serum levels of thyroglobulin (TG), T3, T4, and thyroid-stimulating hormone were determined by radioimmunoassay at 4 or 5 weeks posttransplantation and at the end of the experimental time period of 4 months. All animals were autopsied. The grafts were examined by light microscopy and TG immunohistochemistry. Morphologically, the grafts of benign and malignant thyroid tumors showed features overall identical to the original tissue. Conversely, nontoxic nodular colloid goiter and Graves' disease grafts revealed a transformation to normofollicular structures. All benign thyroid grafts showed a stationary growth, as did most differentiated thyroid carcinomas. Tumor take rates in differentiated and in medullary carcinoma were 15%, and in undifferentiated carcinomas, 100%. In the cancer grafts, a correlation between resting phase (period until progressive tumor growth) and survival time of the corresponding patients was disclosed. All patients whose tumors were not taken by nude mice are still alive and show no signs of progressive tumor growth at 9 to 34 months after surgery. All but one patient with tumors revealing positive tumor take died within 3 months (resting phase, 3 weeks) or one year (resting phase, 7 to 14 weeks) after surgery. Integrity of hormonal function in benign and malignant xenografts at 4 months posttransplantation could be shown by significantly higher T3 and T4 serum concentrations in animals with benign thyroid tissues (T3, 1.69 +/- 0.13 nmol/liter; T4, 45.69 +/- 2.09 nmol/liter; S.E.) as compared to controls without grafted tissue [T3, 1.29 +/- 0.10 nmol/liter (p less than 0.05); T4, 33.39 +/- 2.71 nmol/liter (p less than 0.05)] and by increased TG serum concentrations in animals receiving benign (TG, 2.70 +/- 1.39 ng/ml) or malignant (e.g., TG in follicular carcinoma, 34.44 +/- 13.83 ng/ml; controls, 0.30 +/- 0.02 ng/ml) thyroid tissue. Thus, we conclude that benign and malignant thyroid xenografts in the nude mouse maintain full morphological and, regarding T3, T4, and TG serum levels, functional integrity for at least 4 months after transplantation.
取自16例良性甲状腺病变患者（10例非毒性结节性胶样甲状腺肿、2例滤泡性腺瘤、1例自主性腺瘤、1例碘致甲状腺毒症、2例格雷夫斯病）和18例恶性甲状腺肿瘤患者（7例乳头状癌、5例滤泡状癌、5例未分化癌（间变性癌）、1例髓样癌）的组织，被异种移植到124只6周龄同基因雌性BALB/c-nu/nu小鼠的侧腹。随后，在未进行任何进一步治疗的情况下，于移植后4或5周以及4个月实验时间段结束时，通过放射免疫测定法测定血清甲状腺球蛋白（TG）、T3、T4和促甲状腺激素水平。对所有动物进行尸检。通过光学显微镜和TG免疫组织化学检查移植物。形态学上，良性和恶性甲状腺肿瘤的移植物总体上显示出与原始组织相同的特征。相反，非毒性结节性胶样甲状腺肿和格雷夫斯病移植物显示出向正常滤泡结构的转变。所有良性甲状腺移植物以及大多数分化型甲状腺癌移植物均呈现静止生长。分化型癌和髓样癌的肿瘤接种率为15%，未分化癌的肿瘤接种率为100%。在癌移植物中，发现静止期（直至肿瘤进行性生长的时期）与相应患者的生存时间之间存在相关性。所有肿瘤未被裸鼠接种的患者仍然存活，并且在手术后9至34个月没有肿瘤进行性生长的迹象。除1例肿瘤接种阳性的患者外，所有患者均在手术后3个月（静止期3周）或1年（静止期7至14周）内死亡。与未移植组织的对照动物相比，移植后4个月时，良性甲状腺组织动物的T3和T4血清浓度显著升高（T3，1.69±0.13 nmol/升；T4，45.69±2.09 nmol/升；标准误），以及接受良性（TG，2.70±1.39 ng/ml）或恶性（例如滤泡状癌中的TG，34.44±13.83 ng/ml；对照，0.30±0.02 ng/ml）甲状腺组织的动物TG血清浓度升高，这表明良性和恶性甲状腺异种移植物的激素功能在移植后4个月时保持完整。因此，我们得出结论，裸鼠体内的良性和恶性甲状腺异种移植物在移植后至少4个月内保持完整的形态，并且就T3、T4和TG血清水平而言，保持功能完整性。
