Basic and clinical studies on an overcome of drug resistance inchemotherapy for heas and neck cancer

克服头颈癌化疗耐药的基础与临床研究

• 批准号: 04671027
• 负责人: INUYAMA Yukio
• 金额: $ 1.34万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671027/
• 关键词: P-glycoprotein; Head and neck canncer; Mdrl mRNA; Slot blot hybridization; RT-PCR; Cisplatin; Etoposide; Mitomycin C

(1) Basic research : The expression of P-glycoprotein(P-gp) which participates in drug resistance was immunohistochemically examined in 25 cases of malignant tumors of the head and neck. As a result, the expression of P-gp was observed in one case of malignant fibrous hitiocytoma after chemotherapy. And again the expression of P-gp was found in 4 out of 5 cases of adenoid cystic carcinoma even before chemotherapy, which may explain a possibility of natural resistance in these tumors. These facts that P-gp was expressed in some malignant tumors of the head and neck may suggest a correlation between P-gp and drug sensitivity.Then we studied the expression of mdrl at the level of mRNA.The methods used are slot blot hydridization, Northern blot hybridization, and in situ hybridization. The expression of mdr1mRNA was recognized in ISH and RT-PCR even in cases not observed in Northern blot and slot blot hybridization. In some cases, the expression of mdr1mRNA did not coincide with the results of the expression which were shown in immunostain of P-gp.(2) Clinical research : A newly developped regimen consisits of cisplatin(CDDP), etoposide(VP-16), and mitomycin C(MMC). Administration method is as follows : CDD P 60mg/m^2 iv over 2 hours on day 1, VP-16 40mg/m^2 iv over 1 hour on days 1-3, MMC 7mg/m^2 iv bolus on day 1. Complete response was achieved in one case of recurrent laryngeal cancer, although he received VMP therapy (VCR+MTX+REP), CDDP+VP-16, radiotherapy and radical surgery with reconstruction. Biosy was negative after chemotherapy. This result was very encouraging. We will try concurrent chemotherapy and radiotherapy in near future.

(1)基础研究：采用免疫组织化学方法检测25例头颈部恶性肿瘤中参与耐药的P-糖蛋白(P-gp)的表达。结果：1例恶性纤维组织细胞瘤化疗后P-gp表达阳性。在5例腺样囊性癌中，有4例在化疗前仍有P-gp表达，这可能是腺样囊性癌自然耐药的原因。这些P-gp在一些头颈部恶性肿瘤中表达的事实可能表明P-gp与药物敏感性有关。然后，我们从mRNA水平上研究了mdrl的表达。方法有缝隙杂交、Northern杂交和原位杂交。原位杂交和RT-PCR检测到mdr1mRNA的表达，Northern杂交和狭缝杂交检测不到mdr1mRNA的表达。临床研究：由顺铂(CDDP)、依托泊苷(VP-16)和丝裂霉素C(MMC)组成的新方案。给药方法：顺铂60 mg/m2，第1天静脉滴注2小时以上，VP-16 40 mg/m2静脉滴注，第1~3天1小时以上，MMC 7 mg/m2静脉推注，第1天。1例复发性喉癌患者接受VMP治疗(VCR+MTX+REP)、CDDP+VP-16、放疗及根治性手术加重建后完全缓解。化疗后Biosy均为阴性。这一结果非常令人鼓舞。我们将在不久的将来尝试同步化疗和放射治疗。

项目成果

高須 毅.犬山 征夫・他: "頭頚部悪性腫瘍における多剤耐性遺伝子産物の免疫組織学的検索" 頭頚部腫瘍. 18. 54-57 (1992)

Takeshi Takasu、Yukio Inuyama 等人：“头颈恶性肿瘤中多药耐药基因产物的免疫组织学搜索”Head and Neck Tumor. 18. 54-57 (1992)。

犬山征夫他: "化学療法のみで治癒した頭頚部進行癌・再発癌の2症例" Karkinos. 7. 85-90 (1994)

Yukio Inuyama 等人：“仅用化疗治愈两例晚期/复发性头颈癌”Karkinos。7. 85-90 (1994)

犬山征夫: "(特集)頭頚部癌の化学療法,頭頚部癌化学療法の歴史と現況" JOHNS. 9. 549-556 (1993)

Yukio Inuyama：“（专题）头颈癌化疗，头颈癌化疗的历史和现状”JOHNS。 9. 549-556 (1993)

Yukio Inuyama: "Two patients with advanced or recurrent head and neck cancer who were treated with chemotheapy and cured" Karkinos. 7(1). 85 (1994)

Yukio Inuyama：“两名患有晚期或复发性头颈癌的患者接受化疗并治愈”Karkinos。

Yukio Inuyama: "History and current status of chemotherapy for head and neck cancer" JOHNS. 9(9). 549 (1993)

Yukio Inuyama：“头颈癌化疗的历史和现状”JOHNS。