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Cabrini G.,University of Verona | Fabbri E.,University of Ferrara | Lo Nigro C.,S. Croce and Carle Teaching Hospital | Dechecchi M.C.,University of Verona | Gambari R.,University of Ferrara
International Journal of Oncology | Year: 2015

O-6-methylguanine-DNA methyltransferase (MGMT) is an abundantly expressed nuclear protein dealkylating O6-methylguanine (O6-MG) DNA residue, thus correcting the mismatches of O6-MG with a thymine residue during DNA replication. The dealkylating effect of MGMT is relevant not only in repairing DNA mismatches produced by environmental alkylating agents promoting tumor pathogenesis, but also when alkylating molecules are applied in the chemotherapy of different cancers, including glioma, the most common primary tumor of the central nervous system. Elevated MGMT gene expression is known to confer resistance to the treatment with the alkylating drug temozolomide in patients affected by gliomas and, on the contrary, methylation of MGMT gene promoter, which causes reduction of MGMT protein expression, is known to predict a favourable response to temozolomide. Thus, detecting expression levels of MGMT gene is crucial to indicate the option of alkylating agents or to select patients directly for a second line targeted therapy. Further study is required to gain insights into MGMT expression regulation, that has attracted growing interest recently in MGMT promoter methylation, histone acetylation and microRNAs expression. The review will focus on the epigenetic regulation of MGMT gene, with translational applications to the identification of biomarkers predicting response to therapy and prognosis. Source

Garrone O.,S. Croce and Carle Teaching Hospital | Bertelli G.,Singleton Hospital | Principe E.,oce And Carle University Hospital | Lewis P.D.,University of Swansea | And 3 more authors.
Tumori | Year: 2014

Aim and background. A reduction of gynaecological adverse events has been reported in trials comparing aromatase inhibitors with tamoxifen as adjuvant treatment in postmenopausal women with early breast cancer, but there is a paucity of randomised studies specifically investigating their effects on the uterus. We report here the results of a prospective phase III trial comparing the effects of tamoxifen and exemestane by transvaginal ultrasound (TVUS). Patients and methods. Postmenopausal patients with ER+ early breast cancer were randomised to receive tamoxifen 20 mg once daily or exemestane 25 mg once daily as adjuvant hormone therapy. TVUS was performed at baseline and at 6 and 12 months to measure endometrial thickness (ET) and uterine volume (UV). Results. A total of 123 women were randomised to tamoxifen (n = 61) or exemestane (n = 62). A significantly higher proportion of patients in the tamoxifen group had increased ET at 6 and 12 months from randomisation compared with the exemestane group (66.1% and 64.3% versus12.1% and 6.8%, respectively; P <0.0001). Mean ET and UV also significantly increased with tamoxifen compared to exemestane at both time points (P <0.01 for all comparisons). Conclusion. Tamoxifen is associated with endometrial thickening and increased uterine volume in a significant proportion of postmenopausal women with early breast cancer. Our study confirms the lack of endometrial effects of exemestane, which may be of interest to patients and clinicians when choosing among adjuvant endocrine options for breast cancer. Source

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