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小鼠C1300神经母细胞瘤术前和术后联合免疫治疗

Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma.

作者信息

Fowler C L, Brooks S P, Rossman J E, Cooney D R

机构信息

Section of Pediatric Surgery, University of Kentucky Medical Center, Lexington 40536-0084.

出版信息

J Pediatr Surg. 1993 Mar;28(3):420-6; discussion 426-7. doi: 10.1016/0022-3468(93)90242-d.

DOI:10.1016/0022-3468(93)90242-d
PMID:8468657
Abstract

Preoperative treatment of murine C1300-neuroblastoma (C1300) with triple immunotherapy using low-dose cyclophosphamide (CY), retinyl palmitate (RP), and interleukin-2 (IL2), followed by tumor resection leads to significant initial tumor control and prolonged survival. However, because long-term tumor recurrence is 67%, the efficacy of continued postoperative immunotherapy is now evaluated. Thirty-two A/J mice with 1 cm subcutaneous C1300 tumors were treated for 13 days with CY-100 mg/kg, intraperitoneally (IP), on day 2 of treatment then 25 mg/kg on day 9, RP-2500 IU IP 2 x/week, and IL2 1.6 x 10(5) U IP BID on days 4 to 9 and 11 to 13. On day 14, mice were divided into five treatment groups: (1) OP (operated-tumor resection, n = 6); (2) OP+CY (resection and postoperative CY, n = 7); (3) OP+CY+RP (resection and postoperative CY+RP, n = 7); (4) OP+CY+RP+IL2 (resection and postoperative CY+RP+IL2, n = 7); and (5) CY+RP+IL2 (continued CY+RP+IL2 with no resection, n = 5). Survival and postoperative tumor recurrence were followed for 60 days. The cure rates were group 1 33% (2/6), group 2 43% (3/7), group 3 29% (2/7), group 4 71% (5/7), and group 5 20% (1/5). After surgery, tumors that recurred did so in 8 to 22 days, with no statistical difference noted between groups. MHC class I antigenic expression of tumors resected on day 14 and recurrent tumors was determined with monoclonal antibodies and flow cytometry. In tumors resected on day 14, class I expression measured by mean fluorescence, was 374.8 +/- 27.40.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

使用低剂量环磷酰胺(CY)、棕榈酸视黄酯(RP)和白细胞介素-2(IL2)进行三联免疫疗法对小鼠C1300神经母细胞瘤(C1300)进行术前治疗,随后进行肿瘤切除,可实现显著的初始肿瘤控制并延长生存期。然而,由于长期肿瘤复发率为67%,现对术后持续免疫疗法的疗效进行评估。32只皮下有1厘米C1300肿瘤的A/J小鼠在治疗第2天接受100毫克/千克CY腹腔注射(IP),共治疗13天,第9天剂量减为25毫克/千克,RP为2500国际单位,每周2次IP注射,IL2在第4至9天和第11至13天每天2次、每次1.6×10⁵单位IP注射。第14天,将小鼠分为五个治疗组:(1)OP(手术-肿瘤切除,n = 6);(2)OP+CY(切除并术后用CY,n = 7);(3)OP+CY+RP(切除并术后用CY+RP,n = 7);(4)OP+CY+RP+IL2(切除并术后用CY+RP+IL2,n = 7);(5)CY+RP+IL2(持续用CY+RP+IL2且不切除,n = 5)。观察60天的生存期和术后肿瘤复发情况。治愈率分别为:第1组33%(2/6),第2组43%(3/7),第3组29%(2/7),第4组71%(5/7),第5组20%(1/5)。术后肿瘤复发时间为8至22天,各组间无统计学差异。使用单克隆抗体和流式细胞术测定第14天切除的肿瘤和复发肿瘤的MHC I类抗原表达。在第14天切除的肿瘤中,通过平均荧光测量的I类表达为374.8±27.40。(摘要截断于250字)

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