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小细胞肺癌异种移植中对烷化剂的耐药性与肿瘤分化

Resistance to alkylating agents and tumour differentiation in xenografts of small cell lung cancer.

作者信息

Berman R, Gusterson B, Steel G G

出版信息

Br J Cancer. 1985 May;51(5):653-8. doi: 10.1038/bjc.1985.98.

DOI:10.1038/bjc.1985.98
PMID:2581600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1977064/
Abstract

Small cell bronchial carcinoma (SCC) xenografts with differing sensitivity to cyclophosphamide (CY) were investigated using a variety of techniques. Two xenografts (HX78 and HX88) were relatively sensitive to CY, one xenograft (HX72) was inherently resistant to CY and a fourth xenograft (HX78Cy) was a CY induced resistant subline of HX78 and was unstable when maintained without CY exposure. Conventional light microscopy, cytology and electron microscopy examination of the xenografts revealed appearances consistent with SCC. An antikeratin antibody demonstrated the presence of keratin in the inherent and the induced resistant xenografts (and in the unstable revertant) but not in the two sensitive xenografts; the presence of keratin suggested squamous differentiation. Monolayer culture morphology of the sensitive HX78 and the unstable revertant was anchorage independent with the cells forming floating aggregates; the induced resistant subline of this xenograft (HX78Cy) showed, by contrast, flattened, angular adherent cells. Beta HCG production was detected in the monolayer culture supernatant of sensitive HX78 cells; the level of production of beta HCG was increased in the induced resistant HX78Cy cells. Karyotype and flow cytometry studies were also performed. The morphological responses of small cell lung cancer to treatment are discussed.

摘要

利用多种技术对具有不同环磷酰胺(CY)敏感性的小细胞支气管癌(SCC)异种移植瘤进行了研究。两种异种移植瘤(HX78和HX88)对CY相对敏感,一种异种移植瘤(HX72)对CY固有耐药,第四种异种移植瘤(HX78Cy)是HX78的CY诱导耐药亚系,在无CY暴露的情况下维持时不稳定。对异种移植瘤进行常规光学显微镜、细胞学和电子显微镜检查,发现其表现与SCC一致。一种抗角蛋白抗体显示,固有耐药和诱导耐药的异种移植瘤(以及不稳定的回复株)中存在角蛋白,而两种敏感的异种移植瘤中不存在;角蛋白的存在提示鳞状分化。敏感的HX78和不稳定回复株的单层培养形态不依赖贴壁,细胞形成漂浮聚集体;相比之下,该异种移植瘤的诱导耐药亚系(HX78Cy)显示扁平、有角的贴壁细胞。在敏感的HX78细胞单层培养上清液中检测到β-HCG的产生;诱导耐药的HX78Cy细胞中β-HCG的产生水平升高。还进行了核型和流式细胞术研究。讨论了小细胞肺癌对治疗的形态学反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33fe/1977064/b61b64c16609/brjcancer00103-0032-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33fe/1977064/b61b64c16609/brjcancer00103-0032-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33fe/1977064/b61b64c16609/brjcancer00103-0032-a.jpg

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J Cancer Res Clin Oncol. 1995;121(5):309-12. doi: 10.1007/BF01209599.

本文引用的文献

1
Atypical endocrine tumors of the lung.肺非典型内分泌肿瘤
Arch Pathol Lab Med. 1981 Jan;105(1):20-8.
2
Induced and inherent resistance to alkylating agents in human small-cell bronchial carcinoma xenografts.人小细胞支气管癌异种移植瘤对烷化剂的诱导抗性和固有抗性
Br J Cancer. 1984 Apr;49(4):431-6. doi: 10.1038/bjc.1984.69.
3
Tumor marker production in human bronchial carcinoma xenografts.人支气管癌异种移植瘤中的肿瘤标志物产生
Oncodev Biol Med. 1982;3(4):273-81.
4
Treatment of small-cell carcinoma of the lung monitored by sequential flow cytometric DNA analysis.通过连续流式细胞术DNA分析监测的小细胞肺癌治疗
Cancer Res. 1982 Jun;42(6):2499-505.
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The therapeutic response of bronchial carcinoma xenografts: a direct patient-xenograft comparison.支气管癌异种移植的治疗反应:患者与异种移植的直接比较
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Simultaneous demonstration of keratin and mucin.
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Immunohistochemical localisation of keratin in human lung tumours.角蛋白在人肺肿瘤中的免疫组织化学定位
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