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Westborough, MA, United States

Davies M.A.,United Medical Systems
Cancer Discovery

Paradoxical activation of the mitogen-activated protein kinase pathway can cause secondary malignancies in patients treated with inhibitors of BRAF V600 proteins. Characterization of a patient with concurrent BRAF -mutant melanoma and NRAS -mutant leukemia treated intermittently with combined BRAF and MEK inhibition provides new insights into the potential clinical and molecular effects of this therapeutic strategy. © 2014 American Association for Cancer Research. Source

Davies M.A.,United Medical Systems
Cancer Journal

The PI3K (phosphatidylinositol 3-kinase)-AKT pathway is one of the most important signaling networks in cancer. There is growing evidence that activation of this pathway plays a significant role in melanoma, frequently in the setting of concurrent activation of RAS-RAF-MEK-ERK signaling. This evidence includes the identification of genetic and epigenetic events that activate this pathway in melanoma cell lines and clinical specimens. In addition, functional experiments have demonstrated important roles for the PI3K-AKT pathway in both melanoma initiation and therapeutic resistance. The availability of many inhibitors against the PI3K-AKT pathway is rapidly leading to the development of trials that will ultimately determine its clinical significance in this disease. The rational development of such therapies will be facilitated by strategies that utilize the growing understanding of the complexity of the regulation and roles of this pathway. Copyright © 2012 by Lippincott Williams &Wilkins. Source

Abdollahi A.,United Medical Systems | Abdollahi A.,Heidelberg Ion Therapy Center | Folkman J.,Vascular Biology Program
Drug Resistance Updates

Within three decades, anti-angiogenic therapy has rapidly evolved into an integral component of current standard anti-cancer treatment. Anti-angiogenic therapy has fulfilled a number of its earlier proposed promises. The universality of this approach is demonstrated by the broad spectrum of malignant and benign tumor entities, as well as non-neoplastic diseases, that are currently treated with anti-angiogenic agents. In contrast to tumor cell targeting therapies, the development of acquired drug resistance (e.g., via mutations in growth factor receptor signaling genes) has not been described yet for the principal target of anti-angiogenic therapy-the tumor endothelium. Moreover, the tumor endothelium has emerged as a critical target of conventional cancer therapies, such as chemotherapy and radiotherapy. The presumption that tumor growth and metastasis are angiogenesis-dependent implies that the number of potential targets of an anti-cancer therapy could be reduced to those that stimulate the angiogenesis process. Therefore, the set of endogenous angiogenesis stimulants might constitute an "Achilles heel" of cancer. Direct targeting of tumor endothelium via, e.g., endogenous angiogenesis inhibitors poses another promising but clinically less explored therapeutic strategy. Indeed, the majority of current anti-angiogenic approaches block the activity of a single or at most a few pro-angiogenic proteins secreted by tumor cells or the tumor stroma. Based on our systems biology work on the angiogenic switch, we predicted that the redundancy of angiogenic signals might limit the efficacy of anti-angiogenic monotherapies. In support of this hypothesis, emerging experimental evidence suggests that tumors may become refractory or even evade the inhibition of a single pro-angiogenic pathway via compensatory upregulation of alternative angiogenic factors. Here, we discuss current concepts and propose novel strategies to overcome tumor evasion of anti-angiogenic therapy. We believe that early detection of tumors, prediction of tumor evasive mechanisms and rational design of anti-angiogenic combinations will direct anti-angiogenic therapy towards its ultimate goal-the conversion of cancer to a dormant, chronic, manageable disease. © 2009 Elsevier Ltd. All rights reserved. Source

Kwong L.N.,University of Houston | Davies M.A.,United Medical Systems | Davies M.A.,University of Houston

The treatment of melanoma, the most aggressive form of skin cancer, is being revolutionized by the development of personalized targeted therapy approaches. Mutant-selective BRAF inhibitors and MEK inhibitors have demonstrated impressive clinical results in molecularly selected patients. However, emerging understanding of the molecular heterogeneity of this disease and the identification of multiple mechanisms of resistance to targeted therapies strongly support the rationale for combinatorial approaches. In this review, we will discuss the preclinical and clinical studies that are testing leading hypotheses and emerging combinatorial strategies for the future. © 2014 Macmillan Publishers Limited. Source

Fujifilm Co. and United Medical Systems | Date: 2014-07-14

The present invention is directed in general to imaging technologies and more particularly to medical imaging and picture archiving and communication systems (PACS) having an image display wherein system features and functions are provided to a user via active overlays located over displayed images. A system and method are provided to imbed an ability to interact with an image by activating traditional annotations that are displayed in conjunction with an image in a PACS. Users are able to access program functionalities in an improved, quicker, accurate and more intuitive means. More specifically, the present invention relates to providing the capability to customize multiple context menus, and flatten the command hierarchy of an imaging system. The present invention also provides the ability to overload current text and graphic annotations that are already displayed within an image of interest.

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