Antonelli Alessandro, Ferrari Silvia Martina, Fallahi Poupak, Berti Piero, Materazzi Gabriele, Marchetti Ivo, Ugolini Clara, Basolo Fulvio, Miccoli Paolo, Ferrannini Ele
Department of Internal Medicine, School of Medicine, University of Pisa, Via Roma, 67, I-56100 Pisa, Italy.
Eur J Endocrinol. 2008 Sep;159(3):283-91. doi: 10.1530/EJE-08-0190. Epub 2008 Jun 26.
Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures.
To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD).
FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The (V600E)BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without (V600E)BRAF mutation.
Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro.
间变性甲状腺癌(ATC)通常无法手术,化疗和放疗是主要治疗手段。迄今为止,“原发性ATC细胞培养物”(ANA)是从手术活检样本中培养出来的。通过细针穿刺抽吸(FNA-ANA)获取ANA并检测其对不同药物的敏感性,可能会提高治疗效果并避免不必要的手术。
在6例ATC患者手术前获取FNA-ANA,并评估FNA-ANA对化疗药物和噻唑烷二酮(TZD)的化学敏感性。
将6例ATC患者的FNA-ANA在RPMI 1640培养基中培养,并在DMEM中传代。通过用五种不同化疗药物(博来霉素、顺铂、吉西他滨、依托泊苷和卡铂)或TZD(罗格列酮)的递增浓度抑制增殖来评估化学敏感性。化疗药物显著抑制(P<0.0001)FNA-ANA增殖,TZD也是如此(P<0.001);依托泊苷在减少细胞生长方面最有效。从每个患者的活检样本中获得另一种ANA培养物;化学敏感性测试结果与FNA-ANA的结果相似。在2例ATC患者中观察到(V600E)BRAF突变;有或无(V600E)BRAF突变的肿瘤中,药物对增殖的抑制作用相似。
我们的研究表明,1)有可能获得FNA-ANA,并为使用FNA-ANA检测每位患者对不同药物(化疗药物或TZD;可能还有放射敏感性)的化学敏感性开辟了道路,避免了不必要的手术和无效化疗药物的使用;2)依托泊苷在体外能非常有效地减少ATC细胞生长。