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高分化类癌肿瘤的体外化疗耐药性测试。

In vitro chemoresistance testing in well-differentiated carcinoid tumors.

作者信息

Lyons John M, Abergel Jeffrey, Thomson Jessica L, Anthony Cathy T, Wang Yi-Zarn, Anthony Lowell B, Boudreaux J Philip, Strauchen James, Idrees Muhammad, Warner Richard R P, Woltering Eugene A

机构信息

Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

出版信息

Ann Surg Oncol. 2009 Mar;16(3):649-55. doi: 10.1245/s10434-008-0261-z. Epub 2009 Jan 8.

Abstract

BACKGROUND

Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro.

METHODS

Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. (3)H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested.

RESULTS

Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent.

CONCLUSIONS

This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.

摘要

背景

传统上,高分化的“典型”类癌肿瘤对化疗反应很差。我们推测,在体外针对多种抗肿瘤药物进行测试时,高分化类癌肿瘤的标本对化疗的影响具有高度抗性。

方法

手术采集98份典型类癌标本,进行培养并在体外针对抗肿瘤药物进行测试。采用(³H)-胸腺嘧啶核苷掺入法评估受试标本的细胞生长抑制百分比(PCI)。PCI用于确定标本对所测试的每种试剂是否具有极端耐药性(EDR)、中度耐药性(IDR)或低度耐药性(LDR)。

结果

70份标本得出结果。每份标本平均用六种药物进行测试。分类为LDR、IDR和EDR的药物的平均比例分别为0.48(范围0 - 1)、0.34(范围0 - 1)和0.18(范围0 - 0.80)。每份标本表现出LDR、IDR和EDR化疗耐药性的药物平均数量分别为2.7、2.1和1.2。70份标本中有57份(81%)对至少两种药物具有LDR。5-氟尿嘧啶的低化疗耐药频率最高,为69%,其次是阿霉素,为67%。在典型类癌中,对化疗药物的低体外耐药性普遍存在,而EDR相对较少见。

结论

这意味着典型类癌肿瘤的临床化疗耐药性可能比先前临床试验所显示的要少,化疗敏感性更高。这些发现值得进一步研究评估类癌肿瘤对检测指导化疗方案的反应。

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