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转化生长因子-β3介导的细胞周期调控及5-氟尿嘧啶诱导的口腔黏膜炎的减轻

Transforming growth factor-beta 3 mediated modulation of cell cycling and attenuation of 5-fluorouracil induced oral mucositis.

作者信息

Sonis S T, Van Vugt A G, Brien J P, Muska A D, Bruskin A M, Rose A, Haley J D

机构信息

Department of Oral Medicine, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.

出版信息

Oral Oncol. 1997 Jan;33(1):47-54. doi: 10.1016/s0964-1955(96)00043-7.

DOI:10.1016/s0964-1955(96)00043-7
PMID:9192553
Abstract

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which derives from damage to the epithelial cell layer. We have shown that transforming growth factor-beta 3 (TGF-beta 3) negatively regulates epithelial cell proliferation and reduces the incidence of oral mucositis. Here, we report the findings of a large study examining the effects of TGF-beta 3 administration in a hamster model on oral epithelial cell cycling in vivo, on oral mucositis, on weight retention and on survival. Topical application of TGF-beta 3 to the buccal mucosa significantly reduced basal cell proliferation, as measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and DNA ploidy. Administration of topical TGF-beta 3 prior to chemotherapy with 5-fluorouracil (5-FU) significantly reduced the severity of mucositis with respect to time, reduced chemotherapy-associated weight loss and increased survival.

摘要

黏膜炎是接受癌症化疗患者中常见的剂量限制性并发症,它源于上皮细胞层的损伤。我们已经表明,转化生长因子-β3(TGF-β3)对上皮细胞增殖具有负调节作用,并降低口腔黏膜炎的发生率。在此,我们报告一项大型研究的结果,该研究考察了在仓鼠模型中给予TGF-β3对体内口腔上皮细胞周期、口腔黏膜炎、体重维持和生存的影响。通过增殖细胞核抗原(PCNA)免疫组织化学和DNA倍体分析测定,将TGF-β3局部应用于颊黏膜可显著降低基底细胞增殖。在使用5-氟尿嘧啶(5-FU)化疗前给予局部TGF-β3,可在时间方面显著降低黏膜炎的严重程度,减少化疗相关的体重减轻并提高生存率。

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