zearalenone and Esophageal-Neoplasms

Topics: Animals; Carcinogens; China; Diet; Digestive System Neoplasms; Esophageal Neoplasms; Female; Fungi; Fusarium; Humans; Leukemia P388; Mice; Neoplasms; Resorcinols; Selenium; Sesquiterpenes; South Africa; Species Specificity; Trichothecenes; Zearalenone

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

A comparative study on the natural occurrence of Fusarium toxins was done with 47 corn and 30 wheat samples collected in 1989 from Linxian and Shangqiu Counties in Henan Province, People's Republic of China, high- and low-risk areas, respectively, for esophageal cancer. Three trichothecenes (deoxynivalenol [DON], 15-acetyldeoxynivalenol [15-ADON], and nivalenol [NIV]) and zearalenone (ZEA) were detected in corn samples, and DON, NIV, and ZEA were found in wheat samples. Compared with Shangqiu corn, the incidence and mean level of DON in Linxian were 2.4 and 5.8 times higher, respectively, and those of 15-ADON were 16.3 and 2.6 times higher, respectively. The incidence and level of trichothecenes in wheat samples were significantly lower than those in corn. However, the level of DON in Linxian wheat was 3.3 times higher than in Shangqiu wheat. This is the first report indicating a significant difference in the natural occurrence of Fusarium toxins in main staple foods between high- and low-risk areas for esophageal cancer in the People's Republic of China.

Topics: China; Chromatography, Gas; Esophageal Neoplasms; Food Contamination; Fusarium; Gas Chromatography-Mass Spectrometry; Humans; Risk Factors; Trichothecenes; Triticum; Zea mays; Zearalenone

This is the first report to demonstrate the presence of a group of mycotoxins in corn-staple food of Linxian residents, including Nivalenoal (NIV), Deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl-deoxynivalenol (15-ADON), T-2 toxin (these 5 toxins belong to trichothecenes) and zearalenone (ZEN). These 6 toxins were produced by Fusarium species. Using TLC, HPLC, GC, monoclonal antibody affinity column chromatography combined with RIA, respectively, 107 corn samples from Linxian and 2 rice samples from USA were analyzed. It was demonstrated that the average level of NIV was 757 +/- 707(54-2,760)ng/g, DON was 5,376 +/- 4,460 (360-12,670) ng/g with 100% positivity in corn samples consumed as staple food by esophageal cancer patients and their families. Corn samples collected from 5 villages in Linxian at different seasons in 1984-1986 all showed high levels of NIV and DON with 100% positivity which suggested that NIV and DON were consistently and widely existed in Linxian corn samples. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g. This paper also first demonstrates that the extracts of corn from esophageal cancer patients' families and their NIV and DON fractions purified by HPLC could induce significant chromosome aberrations in V79 cells, indicating that they had carcinogenic potential. Pure toxins of NIV, DON, T-2 and 3-ADON could induce chromosome aberrations in V79 cells starting from 1 ng/ml-a very low concentration. When concentrations increased to certain range they all showed toxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cardia; Esophageal Neoplasms; Humans; Mycotoxins; Sesquiterpenes; Stomach Neoplasms; Trichothecenes; Zea mays; Zearalenone

This is the first report of the natural coexistence of a group of Fusarium mycotoxins (nivalenol [NIV], deoxynivalenol [DON], 3-acetyl-deoxynivalenol [3-ADON], 15-acetyl-deoxynivalenol [15-ADON], and zearalenone [ZEN]) in corn from Linxian, China, an area with a high risk of esophageal cancer. Using thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), and gas chromatography (GC), 107 corn samples from Linxian were analyzed. The average levels of NIV and DON were 757 +/- 707 (54-2,760) ng/g and 5,376 +/- 4,460 (360-12,670) ng/g, respectively, with 100% positivity in 24 corn samples consumed as staple food by esophageal cancer patients and their families. Other corn samples collected from five villages in Linxian at different seasons in 1984-1986 also revealed high levels of NIV and DON contamination, with 100% positivity, suggesting that they are consistently and widely present in corn in that area. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g, respectively. Crude extracts of corn samples collected from esophageal cancer patients' families and the HPLC-purified NIV and DON fractions induced significant chromosome aberrations in V79 cells. Pure toxins of NIV, DON, T-2, and 3-ADON also induced chromosome aberrations in V79 cells at very low concentrations (ng levels/ml medium). Cytotoxic effects were observed at slightly higher concentrations. The levels and kinds of trichothecenes were in positive co-relation with the incidence of esophageal cancer. The data suggest that trichothecenes in food may possibly be associated with esophagitis and esophageal cancer in Linxian.

Topics: China; Dose-Response Relationship, Drug; Esophageal Neoplasms; Fusarium; Humans; Mutagenicity Tests; Mycotoxins; Resorcinols; Sesquiterpenes; Trichothecenes; Zea mays; Zearalenone