Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Antonelli
Alessandro
A
Department of Internal Medicine, School of Medicine, University of Pisa, Via Roma, 67, I-56100 Pisa, Italy. a.antonelli@med.unipi.it
Ferrari
Silvia Martina
SM
Fallahi
Poupak
P
Berti
Piero
P
Materazzi
Gabriele
G
Marchetti
Ivo
I
Ugolini
Clara
C
Basolo
Fulvio
F
Miccoli
Paolo
P
Ferrannini
Ele
E
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf