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Rubin M.A.,Precision for Medicine | Rubin M.A.,New York Medical College
Urologic Oncology: Seminars and Original Investigations | Year: 2015

The promise of precision cancer medicine is that we will be able to pair clinical and genomic data to provide better and more efficient treatment for cancer care. Although the focus is on the optimal pairing of existing Food and Drug Administration-approved drugs with the patient[U+05F3]s tumor, precision medicine should also help determine a patient[U+05F3]s risk for disease progression. Precision medicine will hopefully also lead to improved molecular biomarkers. The specific needs for predictive biomarkers vary significantly based on cancer type. The chief aim for prostate cancer biomarker development is to help distinguish indolent from aggressive disease. © 2014 Elsevier Inc.

Ci W.M.,Precision for Medicine | Liu J.,Chinese Academy of Sciences
Physiology | Year: 2015

5-Methylcytosine (5mC) is a major epigenetic modification in animals. The programming and inheritance of parental DNA methylomes ensures the compatibility for totipotency and embryonic development. In vertebrates, the DNA methylomes of sperm and oocyte are significantly different. During early embryogenesis, the paternal and maternal methylomes will reset to the same state. Herein, we focus on recent advances in how offspring obtain the DNA methylation information from parents in vertebrates. ©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07–3.26, P = 2 × 10-16). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01–HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Rubin M.A.,Precision for Medicine | Rubin M.A.,New York Medical College
Cancer Discovery | Year: 2014

Lucas and colleagues nominate transmembrane serine protease type II (TMPRSS2) as an important player in the initiation of epithelial-mesenchymal transition (EMT) in prostate cancer. Cancer cells maintain androgen receptor-regulated cytoplasmic TMPRSS2 expression, which facilitates EMT invasion and metastasis in model systems through hepatocyte growth factor and c-MET signaling. In addition to providing a rationale for potentially targeting this organ-specific enabler of metastatic disease progression, this study also highlights the importance of understanding how organ/tissue-specifi c genes are co-opted in the context of cancer. © 2014 American Association for Cancer Research.

Rosell R.,Precision for Medicine | Karachaliou N.,University of Barcelona
Nature Reviews Gastroenterology and Hepatology | Year: 2015

In 2014, developments in our understanding of escape signaling circuits implicated in resistance to targeted agents in patients with lung cancer have led to improvements in tackling such resistance. The potential role for PET in the management of erlotinib therapy, novel combination therapies and pharmacogenomic-driven individualization of platinum-based chemotherapy represent other key advances. © 2015 Macmillan Publishers Limited.

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