This project aims to correlate the clinical response of gastric and esophageal adenocarcinoma to combination chemotherapy with the presence or absence of various drug resistance markers in fresh tissue samples taken before and after in vivo chemotherapy exposure. An Illinois Cancer Council multicenter phase II trial of a combination of cisplatin, doxorubicin, and etoposide in gastric and esophageal adenocarcinoma will generate clinical data regarding response to chemotherapy. Patients of all stages will be treated, and response endpoints will be standard phase II lesion measurements by imaging and clinical means as well as pathological examination of endoscopic and surgical specimens resected after pre-operative chemotherapy. Expression of the multidrug resistance MDR1 (P-glycoprotein) gene will be analyzed by highly sensitive techniques including cDNA-PCR analysis of mRNA, immunohistochemical staining i, of P-glyroprotein, and functional assays for P-glycoprotein-mediated efflux. cDNA-PCR assays for other genes tentatively associated with drug resistance will also be performed. Correltation between response status and both presence of and levels of gene expression will be made. In addition, correlation between gene expression and the stage and grade of disease will be determined. Immunohistochemical assessment of paraffin-embedded tumor tissue will be done to compare the in vitro gene product analyses with more traditional immunohistochemical markers of gastrointestinal adenocarcinoma.
| Levine, E A; Holzmayer, T; Bacus, S et al. (1997) Evaluation of newer prognostic markers for adult soft tissue sarcomas. J Clin Oncol 15:3249-57 |
| Levine, E A; Holzmayer, T A; Roninson, I B et al. (1993) MDR-1 expression in metastatic malignant melanoma. J Surg Res 54:621-4 |
