Targeting MYCN IRES in -amplified neuroblastoma with inhibits tumor growth and sensitizes tumor cells to radiation
The MYCN oncogene is amplified in 20% of neuroblastomas, leading to its overexpression at both the mRNA and protein levels. MYCN overexpression is strongly associated with advanced disease stage, rapid tumor progression and a worse prognosis. In the present study, we identified microRNA-375 (miRNA-375) as a negative regulator of MYCN: enforced expression of miRNA-375 inhibited MYCN-amplified neuroblastoma in vitro and in vivo. Upon searching the website miRbase for possible miR-375 binding sites within the whole MYCN mRNA, we found that the MYCN 5’-UTR had significant sequence complementarity to miR-375, yet no complemen...
Source: Molecular Oncology - March 24, 2015 Category: Cancer & Oncology Authors: Hailong Zhang, Tao Liu, Sha Yi, Lubing Gu, Muxiang Zhou Source Type: research

Robust -like classification of copy number profiles of samples repeated across different datasets and platforms
Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be ‘BRCA1-like’ or ‘non-BRCA1-like’, which refers to resembling a BRCA1-mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of the BRCA1-like breast cancers have a BRCA1 mutation, one third has hypermethylation of the BRCA1 promoter and one third has an unknown reason for being BRCA1-like. This classification is indicative of patients’ response to high dose alkylating and platinum containing chemotherapy regimens, which targ...
Source: Molecular Oncology - March 21, 2015 Category: Cancer & Oncology Authors: Philip C. Schouten, Anita Grigoriadis, Thomas Kuilman, Hasan Mirza, Johnathan A. Watkins, Saskia A. Cooke, Ewald van Dyk, Tesa M. Severson, Oscar M. Rueda, Marlous Hoogstraat, Caroline Verhagen, Rachael Natrajan, Suet-Feung Chin, Esther H. Lips, Janneke K Source Type: research

Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion
Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for most cancers, hyperactivity of Nrf2 is observed, and siRNA studies assigned Nrf2 as therapeutic target. However, the cancer-protective role of Nrf2 in healthy cells highlights the requirement for an adequate therapeutic window. We engineered artificial transcription factors to assess the role of Nrf2 in healthy (OSE-C2) and malignant ovarian cells (A2780). (Source: Molecular Oncology)
Source: Molecular Oncology - March 21, 2015 Category: Cancer & Oncology Authors: Monique G.P. van der Wijst, Christian Huisman, Archibold Mposhi, Gerard Roelfes, Marianne G. Rots Source Type: research

The Brave New World of Clinical Cancer Research: Adaptive Biomarker-driven Trials Integrating Clinical Practice with Clinical Research
This article describes two designs that are being explored today: platform trials and basket trials. Both are attempting to merge clinical research and clinical practice. (Source: Molecular Oncology)
Source: Molecular Oncology - March 11, 2015 Category: Cancer & Oncology Authors: Donald Berry Tags: Review Source Type: research

Innovative clinical trials for development of personalized cancer medicine
The cancer burden is increasing globally due in large part to the ageing of the population. A major challenge for healthcare systems is an increasing population of cancer patients who are not cured but are living longer with their cancer, making cancer into one of the major chronic diseases and one that carry a high economic burden due to the high cost of many cancer therapies. Innovative approaches to cancer prevention will be able to decrease some of these challenges. Developing better treatment strategies for disseminated disease remains one of the main goals to modify the growing patient population with chronic cancer ...
Source: Molecular Oncology - March 6, 2015 Category: Cancer & Oncology Authors: John Mendelsohn, Ulrik Ringborg, Richard Schilsky Source Type: research