Codegoni A M, Landoni F, Lomonico S, Losa G, Mangioni C, Taverna M, Lucchini V, D'Incalci M
Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Cancer. 1996 Aug 1;78(3):448-53. doi: 10.1002/(SICI)1097-0142(19960801)78:3<448::AID-CNCR11>3.0.CO;2-Z.
The induction of estrogen and progesterone receptors (ER and PGR) has been reported in breast and endometrial cancer cells exposed to human fibroblast interferon-beta (hIFN-beta). Clinical verification of this finding might provide the rationale for new therapeutic approaches. This study was designed to evaluate whether clinical treatment with high doses of hIFN-beta induced ER and PGR in patients with endometrial adenocarcinoma.
Two biopsies were obtained, 1 before and 1 after hIFN-beta treatment (3 x 10(6) i.m. every other day for 3 weeks) from 36 patients with endometrial adenocarcinoma. ER and PGR were determined with standard procedures using radiolabeled ligands.
hIFN-beta treatment did not affect the proportion of ER-positive (i.e., >15 fmol/mg protein) or PGR-positive (i.e., >20 fmol/mg protein) cases. However, in patients with detectable ER and PGR at baseline, hIFN-beta raised the levels. Using a 35% difference before and after therapy as a cut-off, 72 and 79% of cases had increases in ER and PGR, respectively. The difference was highly significant for PGR.
In patients with endometrial adenocarcinoma with undetectable ER or PGR, hIFN-beta did not induce the expression of these receptors. When the receptors were present they were upregulated by hIFN-beta. Whether this increase in receptor levels, particularly PGR, has therapeutic applications remains to be established.
据报道,暴露于人类成纤维细胞干扰素-β(hIFN-β)的乳腺癌和子宫内膜癌细胞中会诱导雌激素和孕激素受体(ER和PGR)的产生。这一发现的临床验证可能为新的治疗方法提供理论依据。本研究旨在评估高剂量hIFN-β的临床治疗是否会诱导子宫内膜腺癌患者的ER和PGR表达。
从36例子宫内膜腺癌患者中,在hIFN-β治疗前和治疗后(每隔一天肌肉注射3×10⁶,共3周)各获取一次活检样本。采用放射性标记配体的标准程序测定ER和PGR。
hIFN-β治疗并未影响ER阳性(即>15 fmol/mg蛋白)或PGR阳性(即>20 fmol/mg蛋白)病例的比例。然而,在基线时可检测到ER和PGR的患者中,hIFN-β提高了其水平。以治疗前后35%的差异作为临界值,分别有72%和79%的病例ER和PGR水平升高。PGR的差异具有高度显著性。
在ER或PGR检测不到的子宫内膜腺癌患者中,hIFN-β不会诱导这些受体的表达。当受体存在时,它们会被hIFN-β上调。受体水平的这种升高,尤其是PGR,是否具有治疗应用价值仍有待确定。