zearalenone and Carcinoma--Squamous-Cell

About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma.. TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma.. In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively).. The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Baculoviral IAP Repeat-Containing 3 Protein; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemoradiotherapy; Cisplatin; Docetaxel; Down-Regulation; Drug Resistance, Neoplasm; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; In Vitro Techniques; Inhibitor of Apoptosis Proteins; Male; MAP Kinase Kinase Kinases; Middle Aged; Neoplasm Proteins; Radiation Tolerance; RNA, Messenger; ROC Curve; Taxoids; Ubiquitin-Protein Ligases; Zearalenone

The effects of zearalenone (F-2), ochratoxin A and T-2 toxins on the synthesis of DNA, RNA and proteins in mouse L cells were studied. F-2 toxin inhibited protein synthesis to a lesser extent than DNA and RNA synthesis, whereas ochratoxin A inhibited the synthesis of each equally. Exposure to the toxins for 24 hours relatively reduced the synthetic ability of the cells. T-2 toxin inhibited protein and DNA synthesis in parallel but RNA synthesis to a lesser extent. Enhanced incorporation of tritiated thymidine was found when L cells were exposed to 0.4 to 0.016 ng of T-2 toxin ml-1 for 24 hours.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line; Cells, Cultured; Humans; L Cells; Laryngeal Neoplasms; Leucine; Mice; Mycotoxins; Ochratoxins; T-2 Toxin; Thymidine; Tritium; Uridine; Zearalenone

A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.

Topics: Animals; Carcinoma, Squamous Cell; Female; Keratins; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Resorcinols; Sesquiterpenes; Skull Neoplasms; T-2 Toxin; Zearalenone