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Identifier |
000401760 |
Title |
Μελέτη συσχέτισης της έκφρασης του γονιδίου ERCC1 σε επίπεδο mRNA και πρωτεϊνης, και των ρυθμιστικών παραγόντων του,με την επιβίωση σε ασθενείς με μη μικροκυτταρικό καρκίνο του πνεύμονα |
Alternative Title |
Correlation study of ERCC1 mRNA protein expression with survival of non-small cell lung cancer |
Author
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Βασάλου, Ελένη
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Thesis advisor
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Μαυρουδής, Δημήτριος
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Reviewer
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Γεωργούλιας, Βασίλειος
Σταθόπουλος, Ευστάθιος
Σαμώνης, Γεώργιος
Θεωδωρόπουλος, Παναγιώτης
Κουτσόπουλος, Αναστάσιος
Σχίζα, Σοφία
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Abstract |
L ung cancer is the leading cause of death from malignant disease in the western world.
Despite its toxicity, platinum-based chemotherapy, has been widely accepted as the
primary treatment of choice in NSCLC. The ERCC1 gene has been implicated in the development
of therapeutic resistance to platinum-based chemotherapy through the nucleotide excision repair
mechanism (NER). In this pathway, ERCC1 binds with the XPF protein to form an endonuclease
complex. This complex is driven to the point of DNA damage through its connection with the
XPA protein. Nonetheless, MZF1 protein has been shown to regulate the expression of ERCC1 as
a transcriptional repressor.
The purpose of this study was to investigate the association of ERCC1, XPF, XPA and MZF1 expression
levels with clinical factors such as response to treatment and survival in patients with
NSCLC.
Overall, 94 patients with advanced stage NSCLC were retrospectively included in the study. All
patients were assessed for the expression of ERCC1 protein by immunohistochemistry, whereas
31 patients were excluded from the study of gene expression due to insufficient biological material.
Of the remaining patients, 63 were successfully amplified for the ERCC1 & XPA genes, 62
for the MZF1 gene, and only 32 for the XPF gene. The expression of all molecular markers was
correlated with clinical and demographic characteristics of patients, response to chemotherapy
and survival.
The results showed that the objective response rate to treatment (RR) was not affected by
the expression of the studied molecular markers. However, low ERCC1 protein expression correlated
with better disease control rate (DCR, p = 0.042) and longer survival (OS, p = 0.045).
Also, the combination of low ERCC1 and high MZF1 gene expression appeared to correlate with
better survival (OS, p = 0.037).
In conclusion, the pharmacogenomic approach could under certain conditions provide a novel
treatment strategy for NSCLC. The ERCC1 protein may have a role in refining prognosis and thus
individualizing chemotherapy in advanced stage NSCLC
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Language |
Greek |
Subject |
Έκφραση |
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Επιβίωση |
Issue date |
2016-07-19 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/2/f/6/metadata-dlib-1473066991-183645-29442.tkl
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Views |
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