Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-Myc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for “malignancy drivers,” which ultimately implement a carcinogenesis process in otherwise healthy mice.

中文翻译：

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人肿瘤源性无细胞滤液对裸鼠的致癌作用

癌症仍然是世界范围内发病和死亡的原因。研究工作包括对健康动物施用肿瘤来源的提取物。之前已经证明，给予小鼠非传染性人类癌症匀浆会诱发恶性肿瘤，在此，我们检查了给予小鼠乳腺癌、胰腺癌和黑色素瘤样品的 50 或 100 µg 粗匀浆蛋白的后果。 2 个月内每周接种 6 次。同时进行的对照小鼠接受了健康供体皮肤整容手术碎片的匀浆。给予乳腺癌匀浆不会引起动物的恶化或死亡。发现了多个肺腺癌病灶，广泛表达恶性组织标志物，并与小细胞样癌共存。在淋巴结中检测到经典上皮标记物呈阳性的播散细胞。胰腺肿瘤和黑色素瘤匀浆的施用逐渐恶化动物健康。胰腺肿瘤诱发低分化肺腺癌和胰岛增生。黑色素瘤影响肺部出现实性假乳头状腺癌。还观察到巨大的非典型肝细胞。肾脏在促纤维增生基质内表现出分散的肿瘤细胞灶。在表皮细胞中发现核重叠、深染核、有丝分裂像和明显的核异型性。在对照小鼠中没有检测到这些变化。此外，斑马鱼胚胎与乳腺肿瘤匀浆一起孵育诱导了cM的表达yc和 HER-2 作为肿瘤标志物，与暴露于健康组织来源材料的胚胎形成对比。这项研究证实并扩展了我们的假设，即肿瘤匀浆含有并可能充当“恶性肿瘤驱动因素”的载体，最终在其他健康的小鼠中实现致癌过程。