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01-01-2019 | Original Article

Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET

Authors: Susumu Hijioka, Keiichiro Sakuma, Masahiro Aoki, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Kazuo Hara, Yasushi Yatabe

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2019

Abstract

Purpose

This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs).

Methods

To test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines.

Results

The cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P = 0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin.

Conclusions

We observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.

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Title: Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET
Authors: Susumu Hijioka
Keiichiro Sakuma
Masahiro Aoki
Nobumasa Mizuno
Takamichi Kuwahara
Nozomi Okuno
Kazuo Hara
Yasushi Yatabe
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3700-y

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