Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purpose: There is currently a lack of validated predictors for adjuvant chemotherapy efficacy in patients with gastric cancer (GC). Perineural invasion (PNI) is the process of neoplastic invasion of the nerves, accompanied by tumor microenvironment (TME) changes. TME can determine treatment outcome while the impact of PNI on chemotherapy efficacy remains unknown in GC. We investigated the association between PNI and the efficacy of postoperative adjuvant chemotherapy in patients with resected GC. Methods: Patients who underwent radical resection of stage IB-III GC with or without fluoropyrimidine (FU)-based adjuvant chemotherapy were retrospectively selected from two separate patient cohorts. PNI was confirmed with S100 immunohistochemistry (IHC). Tumor hypoxia and activity of selected pathways were quantified by mRNA-based signature scoring based on publicly available data. A hypoxia biomarker, ERO1A, and a FU resistance biomarker, thymidylate synthase (TS), were assessed by IHC, respectively. Results: Two cohorts included 223 and 599 patients, respectively. Adjuvant chemotherapy significantly improved overall survival (OS) and disease-free survival (DFS) in PNI-positive but not in PNI-negative patients, which was not impacted by stages. Multivariate models showed that adjuvant chemotherapy was an independent predictor for OS and DFS in PNI-positive patients in both cohorts. For TME, PNI-negative tumors were more hypoxic than were PNI-positive tumors, and displayed relative up-regulation of signaling along the pathways that are important in FU metabolism or resistance. Expressions of ERO1A and TS significantly decreased in PNI-positive compared to PNI-negative tumors. Conclusions: PNI might help predict adjuvant chemotherapy benefit in patients with resected GC. Validation in prospective studies is required. Novel treatment strategies need to be developed in PNI-negative patients.
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PMID:Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer. 3237 27

Background: Thymidylate synthase is one of the target enzymes of 5-fluorouracil. However, the clinical and prognostic significance of TS expression in gastric cancer has remained controversial. In this study, the expression of thymidylate synthase was evaluated in gastric cancer patients treated with combinational chemotherapy; moreover, the association between TS expression and clinicopathologic characteristics and overall survival of the patients were also assessed. Materials and Methods: In this descriptive study, 89 pathological samples were gathered from patients at Kermanshah hospitals during 2008-2017. The survival status of patients was recorded and their overall survival was evaluated individually. Results: The average survival period for low and high thymidylate synthase groups was 54 and 50 months, respectively, meaning higher survival time in the lower thymidylate group. But this difference was not statistically significant (log Rank=0.88). In addition, sex, stage, recurrence, and survival had no significant difference between the low and high expression of thymidylate synthase groups (p=0.89). Conclusion: The results clearly indicated that the level of thymidylate synthase is not a significant modulator of 5- fluorouracil in gastric cancer patients. Nevertheless, evaluation of the level of the enzymes and markers as well as their effects are highly recommended for accurate selection of chemotherapeutical strategies.
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PMID:Relationship between the Expression of the Thymidylate Synthase and the Prognosis of Gastric Cancer Patients Treated with Combinational Chemotherapy Regimen Including Fluorouracil, Docetaxel and Cisplatin. 3302 25


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