The mechanisms involved in the estrogen action on the development and proliferation of oral disease

雌激素对口腔疾病发生和增殖的作用机制

• 批准号: 09672073
• 负责人: OZONO Satoru
• 金额: $ 1.92万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672073/
• 关键词: estrogen receptor; ameloblastoma; adenoid cystic carcinoma; human; DMBA; submandibular gland tumor; rat; in situ hybridization法; 口腔病変; プロゲステロン受容体

Immunohistochemical analysis of estrogen receptor was carried out in salivary adenoid cystic carcinoma and ameloblastoma. In addition, we have tested the presence or absence the antitumor activity of the antiestrogen, tamoxifen, using the DMBA rat submandibular gland tumor model.In these specimens, in agreement with the results seen with the breast cancer tissue used as positive control, strongly-stained cells, in which the ER-immunoreactivity was located in the cell nucleus, were detected. Accordingly, the cases were classed as ER-positive or ER-negative by scoring them on the basis of the visually estimated percentage of tumor cells showing positive nuclear staining, followed by an evaluation using a 10% cut-off level. In human tumors, ER immunoreactivity was positive in 5 (41.7% of total cases ; 3 female and 2 male) of 12 cases of salivary ACC, 11(50% of total cases ; 6 female and 5 male) of 22 cases of ameloblastoma, and one case (female) ot malignant ameloblastoma. The metastatic tumors, which had obtained from the patients with ER positive tumors, showed also immunoreactivity in a large proportion of the tumor cells.In separate experiments, the antitumor effects of tamoxifen, an antiestrogen drug, on DMBA-induced ER-positive submandibular gland tumor in rats were studied. Submandibular gland tumors appeared from about 3 months after transplantation of DMBA pellet to female rats, and more than half of them were ER positive. Tamoxifen inhibited the growth of DMBA-induced ER-positive submandibular gland tumors in rats. Thus, this anti-tumor agent might have clinical potential for use against ER-positive salivary adenoid cystic carcinomas.These results, showing ER expression in human salivary adenoid cystic carcinomas and malignant ameloblastoma, suggest that the presence of this receptor is one of the most useful tools for predicting the response to endocrine therapy for these tumors with poor prognosis

对涎腺样囊性癌和成釉细胞瘤的雌激素受体进行免疫组化分析。此外，我们还利用DMBA大鼠颌下腺肿瘤模型，检测了抗雌激素他莫昔芬的存在或不存在的抗肿瘤活性。在这些标本中，与作为阳性对照的乳腺癌组织的结果一致，检测到强烈染色的细胞，其中er免疫反应性位于细胞核中。因此，根据肉眼估计的核染色阳性的肿瘤细胞百分比，将病例分为er阳性或er阴性，然后使用10%的截止水平进行评估。在人类肿瘤中，12例唾液型ACC中有5例（41.7%，女性3例，男性2例）ER免疫反应阳性，22例成釉细胞瘤中有11例（50%，女性6例，男性5例）ER免疫反应阳性，恶性成釉细胞瘤中有1例（女性）阳性。来自ER阳性肿瘤患者的转移性肿瘤，在很大比例的肿瘤细胞中也表现出免疫反应性。通过单独实验，研究了抗雌激素药物他莫昔芬对dba诱导的er阳性大鼠颌下腺肿瘤的抗肿瘤作用。雌性大鼠DMBA颗粒移植后约3个月开始出现颌下腺肿瘤，且半数以上为ER阳性。他莫昔芬抑制dmba诱导的er阳性大鼠颌下腺肿瘤的生长。因此，这种抗肿瘤药物可能具有临床应用于er阳性唾液腺样囊性癌的潜力。这些结果显示，ER在人唾液腺样囊性癌和恶性成釉细胞瘤中表达，表明该受体的存在是预测这些预后不良肿瘤对内分泌治疗反应的最有用的工具之一

项目成果

小園 知: "エナメル上皮腫における性ホルモン・レセプターの発現について" 日本病理学会誌. 86・1. 266 (1997)

Satoshi Kozono：“成釉细胞瘤中性激素受体的表达”日本病理学会杂志86・1（1997）。

Inoue, S., Kinoshita, Y., Honma, Y., Mizunuma, H.and Ozono, S.: "A case of secondary syphilis with eruption of oral mucosa." J Jpn Oral Muco Membr. 4. 69-73 (1998)

Inoue, S.、Kinoshita, Y.、Honma, Y.、Mizunuma, H. 和 Ozono, S.：“一例口腔粘膜出疹的二期梅毒”。

Ozono, S., Ito, Y., Kubota, N.and Sato, K.: "Expression of sex-hormone receptor in ameloblastoma." Proc Jpn Soc Pathol. 86(1). 266 (1997)

Ozono, S.、Ito, Y.、Kubota, N. 和 Sato, K.：“成釉细胞瘤中性激素受体的表达”。

Ito, Y., Sato, K.and Ozono, S.: "The expression of estrogen and progesterone receptor in sialoadenitis." J.Oral Pathol.Med.27(7). 357 (1998)

Ito, Y.、Sato, K. 和 Ozono, S.：“唾液腺炎中雌激素和孕激素受体的表达。”

Yamamoto,T.: "Origin of primary sensory neurons innervating the buccal stretch receptor"J.Dent.Res.. 78・1. 49-53 (1999)

Yamamoto, T.：“支配颊牵张受体的初级感觉神经元的起源”J.Dent.Res.. 78・1（1999）。