Wilson A P, Ford C H, Newman C E, Howell A
Oncology Research Laboratory, Derby City Hospital, UK.
Br J Cancer. 1987 Dec;56(6):763-73. doi: 10.1038/bjc.1987.285.
A study on the in vitro sensitivity of tumour cells from patients with ovarian cancer has been carried out in parallel with a clinical study designed to evaluate the role of high-dose cis-platinum (CIS) as first-line chemotherapy. A total of 50 samples from 102 patients have been successfully cultured and screened for in vitro chemosensitivity to 7 drugs, including CIS. The malignant nature of cells growing in culture was confirmed using a combination of karyology, morphology and immunohistochemical staining with HMFG2. Tumours were graded as sensitive (less than 40% of control 3H-leucine incorporation), intermediate (41-60% of control) or resistant (greater than 61% of control) to CIS. Correlation of in vitro sensitivity to cis-platinum with clinical response to cis-platinum assessed using CT scan and second-look laparotomy, showed positive correlation in 9/11 (89%) patients (8 = S/S; 1 = R/R); positive correlation between in vitro sensitivity to phosphoramide mustard and clinical response was also found in 4/6 patients receiving cyclophosphamide (3 = S/S; 1 = R/R). All patients with sensitive tumours showed a clinical response to cis-platinum. Comparison of cis-platinum sensitivity with sensitivity to phosphoramide mustard and melphalan showed that some tumours were sensitive only to cis-platinum; resistance to cis-platinum and sensitivity to phosphoramide mustard/melphalan was an infrequent occurrence. Some tumours which were resistant to cis-platinum showed sensitivity to adriamycin and bleomycin, particularly those from untreated patients. Sensitivity to 5-fluorouracil and resistance to cis-platinum was found in approximately equal proportions of tumours in both the treated and untreated groups.
一项关于卵巢癌患者肿瘤细胞体外敏感性的研究与一项旨在评估高剂量顺铂(CIS)作为一线化疗药物作用的临床研究同时进行。从102例患者中总共成功培养了50个样本,并对其进行了对包括CIS在内的7种药物的体外化学敏感性筛查。使用核型分析、形态学以及HMFG2免疫组织化学染色相结合的方法,确认了培养中生长的细胞的恶性性质。肿瘤被分为对CIS敏感(对照3H-亮氨酸掺入量的40%以下)、中度敏感(对照的41%-60%)或耐药(对照的61%以上)。通过CT扫描和二次剖腹探查评估的体外对顺铂的敏感性与对顺铂的临床反应之间的相关性显示,9/11(89%)的患者呈正相关(8例为敏感/敏感;1例为耐药/耐药);在接受环磷酰胺治疗的4/6患者中,体外对环磷酰胺的敏感性与临床反应之间也发现了正相关(3例为敏感/敏感;1例为耐药/耐药)。所有肿瘤敏感的患者对顺铂均表现出临床反应。顺铂敏感性与对环磷酰胺和马法兰敏感性的比较表明,一些肿瘤仅对顺铂敏感;对顺铂耐药而对环磷酰胺/马法兰敏感的情况很少见。一些对顺铂耐药的肿瘤对阿霉素和博来霉素敏感,尤其是来自未治疗患者的肿瘤。在治疗组和未治疗组中,对5-氟尿嘧啶敏感而对顺铂耐药的肿瘤比例大致相等。