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| Thymidylate synthase mRNA level in adenocarcinoma of the stomach: A predictor for primary tumor response and overall survival |
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| Author(s): Lenz HJ, Leichman CG, Danenberg KD, Danenberg PV, Groshen S, Cohen H, Laine L, Crookes P, Silberman H, Baranda J, Garcia Y, Li J, Leichman L |
| Source: JOURNAL OF CLINICAL ONCOLOGY Volume: 14 Issue: 1 Pages: 176-182 Published: JAN 1996 |
| Times Cited: 258 References: 27 |
| Abstract: Purpose: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. Patients and Methods: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method, Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m(2)/d administered for 3 weeks with leucovorin 20 mg/m(2)/w. Cisplatin 100 mg/m(2) was administered on day 1.
Results: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001), The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003).
Conclusion: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer, Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.
(C) 1996 by American Society of Clinical Oncology.
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| Document Type: Article |
| Language: English |
Addresses:
1. UNIV SO CALIF, SCH MED, DEPT MED, DIV MED ONCOL, LOS ANGELES, CA 90033 USA 2. UNIV SO CALIF, SCH MED, DEPT MED, DIV GASTROINTESTINAL & LIVER DIS, LOS ANGELES, CA 90033 USA 3. UNIV SO CALIF, SCH MED, DEPT BIOCHEM, LOS ANGELES, CA 90033 USA 4. UNIV SO CALIF, SCH MED, DEPT SURG, LOS ANGELES, CA 90033 USA 5. UNIV SO CALIF, SCH MED, DEPT PATHOL, LOS ANGELES, CA 90033 USA |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Oncology |
| IDS Number: TP687 |
| ISSN: 0732-183X |
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