Abstract | BACKGROUND: METHODS: 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. RESULTS: 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). CONCLUSIONS:
|
Authors | G Piro, S Giacopuzzi, M Bencivenga, C Carbone, G Verlato, M Frizziero, M Zanotto, M M Mina, V Merz, R Santoro, A Zanoni, G De Manzoni, G Tortora, D Melisi |
Journal | British journal of cancer
(Br J Cancer)
Vol. 113
Issue 6
Pg. 878-85
(Sep 15 2015)
ISSN: 1532-1827 [Electronic] England |
PMID | 26291056
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 7-oxozeanol
- Inhibitor of Apoptosis Proteins
- Neoplasm Proteins
- RNA, Messenger
- Taxoids
- Docetaxel
- Zearalenone
- BIRC3 protein, human
- Baculoviral IAP Repeat-Containing 3 Protein
- Ubiquitin-Protein Ligases
- MAP Kinase Kinase Kinases
- MAP kinase kinase kinase 7
- Cisplatin
- Fluorouracil
|
Topics |
- Adenocarcinoma
(metabolism, pathology, therapy)
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Apoptosis
(drug effects, radiation effects)
- Baculoviral IAP Repeat-Containing 3 Protein
- Carcinoma, Squamous Cell
(metabolism, pathology, therapy)
- Cell Line, Tumor
- Chemoradiotherapy
(methods)
- Cisplatin
(administration & dosage)
- Docetaxel
- Down-Regulation
- Drug Resistance, Neoplasm
- Esophageal Neoplasms
(metabolism, pathology, therapy)
- Esophagogastric Junction
- Female
- Fluorouracil
(administration & dosage)
- Humans
- In Vitro Techniques
- Inhibitor of Apoptosis Proteins
(genetics, metabolism)
- MAP Kinase Kinase Kinases
(antagonists & inhibitors, physiology)
- Male
- Middle Aged
- Neoplasm Proteins
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- ROC Curve
- Radiation Tolerance
- Taxoids
(administration & dosage)
- Ubiquitin-Protein Ligases
(genetics, metabolism)
- Zearalenone
(analogs & derivatives, pharmacology)
|