Luigi Pirtoli1, Giuseppe Belmonte1, Marzia Toscano1, Paolo Tini1, Clelia Miracco2. 1. Tuscan Tumor Institute, Florence, Italy Unit of Radiation Oncology, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy. 2. Tuscan Tumor Institute, Florence, Italy Unit of Pathological Anatomy, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy miracco@unisi.it.
Abstract
BACKGROUND: Glioblastoma (GB) recurrences are rarely removed, therefore, tissue modifications induced by radiotherapy, and temozolomide chemotherapy are scarcely known. Nuclear cyclin D1 is associated with GB progression and resistance to therapy. We previously found that the expression of autophagic protein beclin-1 is a major determinant of prognosis in GB. PATIENTS AND METHODS: In 31 patients with primary GB and their recurrences, we investigated the protein expression of cyclin D1 and beclin-1, before and after radiotherapy-temozolomide therapy by immunohistochemistry. RESULTS: Most (20/31) primary GBs were negative for nuclear cyclin D1, and highly expressed beclin-1. In their recurrences, cytoplasmic cyclin D1 positivity was observable, which co-localized with beclin-1. Eleven primary GBs instead exhibited low beclin-1 expression and were positive for nuclear cyclin D1; three of their recurrences exhibited an increase of beclin-1, which co-localized with cyclin D1 in the cytoplasm. CONCLUSION: Our results suggest therapy-induced degradation of cyclin D1 via autophagy. Copyright
BACKGROUND:Glioblastoma (GB) recurrences are rarely removed, therefore, tissue modifications induced by radiotherapy, and temozolomide chemotherapy are scarcely known. Nuclear cyclin D1 is associated with GB progression and resistance to therapy. We previously found that the expression of autophagic protein beclin-1 is a major determinant of prognosis in GB. PATIENTS AND METHODS: In 31 patients with primary GB and their recurrences, we investigated the protein expression of cyclin D1 and beclin-1, before and after radiotherapy-temozolomide therapy by immunohistochemistry. RESULTS: Most (20/31) primary GBs were negative for nuclear cyclin D1, and highly expressed beclin-1. In their recurrences, cytoplasmic cyclin D1 positivity was observable, which co-localized with beclin-1. Eleven primary GBs instead exhibited low beclin-1 expression and were positive for nuclear cyclin D1; three of their recurrences exhibited an increase of beclin-1, which co-localized with cyclin D1 in the cytoplasm. CONCLUSION: Our results suggest therapy-induced degradation of cyclin D1 via autophagy. Copyright
Authors: Stephanie Andrade; Maria João Ramalho; Maria do Carmo Pereira; Joana A Loureiro Journal: Front Pharmacol Date: 2018-11-20 Impact factor: 5.810