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

(1)基础研究：应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。结果在1例恶性纤维组织细胞瘤化疗后观察到P-gp的表达。在5例腺样囊性癌中有4例发现P-gp的表达甚至在化疗前，这可能解释了这些肿瘤自然耐药的可能性。P-gp在某些头颈部恶性肿瘤中表达，提示P-gp与药物敏感性相关。然后在mRNA水平上研究mdrl的表达。所采用的方法有槽杂交、Northern杂交和原位杂交。mdr1mRNA的表达在ISH和RT-PCR中被识别，即使在Northern blot和slot blot杂交中没有观察到。在某些情况下，mdr1mRNA的表达与P-gp免疫染色显示的表达结果不一致。(2)临床研究：新开发的方案由顺铂（CDDP）、依托泊苷（VP-16）、丝裂霉素C（MMC）组成。给药方法：CDD P 60mg/m^2 iv，第1天2小时，VP-16 40mg/m^2 iv，第1天1小时，MMC 7mg/m^2 iv，第1天。1例喉癌复发患者接受了VMP治疗（VCR+MTX+REP）、CDDP+VP-16、放疗和根治性手术重建，但仍获得完全缓解。化疗后活检呈阴性。这个结果非常令人鼓舞。在不久的将来，我们将尝试同步化疗和放疗。

(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.