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首页> 外文会议>Conference on Small Animal Whole-Body Optical Imaging Based on Genetically Engineered Probes; 20080121-22; San Jose,CA(US) >IMAGING ENHANCEMENT OF MALIGNANCY BY CYCLOPHOSPHAMIDE: SURPRISING CHEMOTHERAPY OPPOSITE EFFECTS
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IMAGING ENHANCEMENT OF MALIGNANCY BY CYCLOPHOSPHAMIDE: SURPRISING CHEMOTHERAPY OPPOSITE EFFECTS

机译：环磷酰胺对恶性肿瘤的影像增强作用：令人惊讶的化学治疗相反效应

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Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.
机译：尽管癌症化学疗法的副作用是众所周知的，但是增强所治疗的癌症的恶性的化学疗法的“相反作用”还不是很清楚。我们已经观察到了许多恶性步骤，这些恶性步骤在人肿瘤细胞移植之前通过化学疗法对小鼠进行了化学预处理。癌细胞诱导血管内增殖，外渗和集落形成，转移的关键步骤通过用常用化学疗法药物环磷酰胺预处理宿主小鼠而得到增强。环磷酰胺似乎干扰了至少抑制某些肿瘤细胞抑制血管内增殖，外渗和血管外集落形成的宿主过程。环磷酰胺不会直接影响癌细胞，因为在注射癌细胞时环磷酰胺已被清除。未经环磷酰胺预处理，人结肠癌细胞在裸鼠的门静脉注射后迅速死亡。癌细胞在6小时内发生广泛的clasmocytosis（细胞质破坏）。注射后12小时内，门静脉内的凋亡细胞数量迅速增加。然而，当用环磷酰胺预处理宿主小鼠时，癌细胞在门静脉注射后存活并在肝脏中形成集落。这些结果表明，对环磷酰胺敏感的宿主细胞系统攻击癌细胞。这篇综述描述了一种重要的，意想不到的化学“相反作用”，它增强了恶性肿瘤的关键步骤，而不是抑制了这些关键步骤，表明应该对某些当前的癌症化疗方法进行修改。

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