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Title: Feasibility of personalized adjuvant chemotherapy of gastric cancer utilizing expression of proteins associated with metabolism and pharmacodynamics of cisplatin and fluorouracyl

Abstract:

Gastric cancer in the western population is associated with poor prognosis. High rates of local and systemic relapse in patients undergoing potentially curative resections indicate the need of systemic therapy. The vast majority of chemotherapy regimens include fluoropirimidines or platinium based agents. These regimens are with some heterogeneity in efficacy and safety. The aim of the study is to analyse a potential relationships between expression of the aforementioned 24 proteins associated with the pharmacokinetics and pharmacodynamics and metabolism of cisplatin and 5-fluorouracil and efficacy as well as safety outcomes of adjuvant chemotherapy of gastric cancer.METHODOLOGYClinical data and specimens were taken from 119 patients with gastric cancer. The group of 24 proteins measured immunohistochemically (IHC). Protein expression were quantified by immunohistochemistry using tissue microarrays. The results were correlated with clinical parameters and efficacy and safety of chemotherapy.RESULTSAmong 119 patients after gastric surgery 50% received adjuvant chemotherapy. Lack of the expression of DPD protein significantly prolonged the median overall survival (OS) time compared to the patients with DPD expression (51 months, 95% CI 17-84 vs 11 months, 95% CI 2-21; P=0,012). Expression of MSH2 protein in tumor cells significantly prolonged the median overall survival (OS) compared to those without expression (25 months, 95% CI 9-42 vs 3 months, 95% CI 0-3; P<0,001). Multivariate analysis revealed that the Karnofsky performance status as well as tumor staging, expression of DPD, radicality of gastric resection were independent prognostic factors for gastric cancer. Cardiovascular diseases was an only statistical significant risk factor for chemotherapy-related toxicity, but not investigated proteins. CONCLUSIONSThese results indicated that among 24 analyzed proteins only the expression of MSH2 and lack of expression od DPD in tumor cells had a significant effect on median overall survival in gastric cancer patients.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia ; choroby układu trawiennego

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Jan Kulig

Date issued:

2018

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:4407

Call number:

ZB-130873

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

Mar 18, 2021

In our library since:

Mar 18, 2021

Number of object content hits:

1

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4408

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Edition name Date
ZB-130873 Mar 18, 2021

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