3,133 research outputs found
The identification of therapeutic targets in metastatic melanoma
No full textMetastatic melanoma, a cancer historically refractory to chemotherapeutic strategies, has a poor prognosis and accounts for the majority of skin cancer related mortality. Although the recent approval of two new drugs combating this disease, Ipilimumab and Vemurafenib (PLX4032), has demonstrated for the first time in decades an improvement in overall survival; the clinical efficacy of these drugs has been marred by severe adverse immune reactions and acquired drug resistance in patients, respectively. Thus, understanding the etiology of metastatic melanoma will contribute to the improvement of current therapeutic strategies while leading to the development of novel drug approaches.\ud
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In order to identify recurrently mutated genes of therapeutic relevance in metastatic melanoma, a panel of stage III local lymph node melanomas were extensively characterised using high-throughput genomic technologies. This led to the identification of mutations in TFG in 5% of melanomas from a candidate gene sequencing approach using SNP array analysis, 24% of melanomas with mutations in MAP3K5 or MAP3K9 though unbiased whole-exome sequencing strategies, and inactivating mutations in NF1 in BRAF/NRAS wild type tumours though pathway analysis. Lastly, this thesis describes the development of a melanoma specific mutation panel that can rapidly identify clinically relevant mutation profiles that could guide effective treatment strategies through a personalised therapeutic approach.\ud
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These findings are discussed in respect to a number of important issues raised by this study including the current limitation of next-generation sequencing technology, the difficulty in identifying ‘driver’ mutations critical to the development of melanoma due to high carcinogenic exposure by UV radiation, and the ultimate application of mutation screening in a personalised therapeutic setting. In summary, a number novel genes involved in metastatic melanoma have been identified that may have relevance for current therapeutic strategies in treating this disease
Whole genome and exome sequencing of melanoma
No full textMelanoma has historically been refractive to traditional therapeutic approaches. As such, the development of novel drug strategies has been needed to improve rates of overall survival in patients with melanoma, particularly those with late stage or disseminated disease. Recent success with molecularly based targeted drugs, such as Vemurafenib in BRAF-mutant melanomas, has now made “personalized medicine” a reality within some oncology clinics. In this sense, tailored drugs can be administered to patients according to their tumor “mutation profiles.” The success of these drug strategies, in part, can be attributed to the identification of the genetic mechanisms responsible for the development and progression of metastatic melanoma. Recently, the advances in sequencing technology have allowed for comprehensive mutation analysis of tumors and have led to the identification of a number of genes involved in the etiology of metastatic melanoma. As the methodology and costs associated with next-generation sequencing continue to improve, this technology will be rapidly adopted into routine clinical oncology practices and will significantly impact on personalized therapy. This review summarizes current and emerging molecular targets in metastatic melanoma, discusses the potential application of next-generation sequencing within the paradigm of personalized medicine, and describes the current limitations for the adoption of this technology within the clinic
Ken Friedenreich Interview
No full textThis interview is an oral history conducted by Linfield College student Camille Weber with Ken Friedenreich. The interview took place at the Jereld R. Nicholson Library at Linfield College on October 16, 2015.
Ken Friedenreich is an author who has written about Oregon wine and its history. The interview includes how he got interested in wine, what it\u27s like to write about wine for a living, the effects that prohibition had on Oregon, and advice for people new to wine
Event Invitation: An Evening with Dr. Ken Robinson
No full textInvitation:
Guest speaker, Dr. Ken Robinson, author of “Out of Our Minds: Learning to be Creative, ” will speak on the importance of arts, the development of creativity, education, and the economy. And, introducing the inaugural DaVinci Scholars Awards program
Ken Wilber's Spectrum Model: Identifying Alternative Soteriological Perspectives
No full textI identify two problematic strands of Wilber's transpersonal theory. First, I question Wilber's claim that his spectrum model is supported by the materials of all the world's major mystical traditions. I argue that his integral, hierarchical perspective privileges some traditions but distorts others. Drawing heavily upon Andrew Rawlinson's recent, taxonomic study of mystical traditions, which identifies four authentic routes to spiritual emancipation (Cool Structured, Cool Unstructured, Hot Structured and Hot Unstructured), I argue that while Wilber's model, itself Cool (the source of spiritual liberation lies within oneself) and Structured (developmental, hierarchical), provides a valuable cartography of transpersonal structures and states of consciousness, it cannot adequately handle the materials of the alternative, soteriological paths of Hot traditions (emphasizing the numinous, and as other than oneself) and Unstructured traditions (affirming that there can be no gradual, or progressive, spiritual development at all). Second, and more cursorily, I argue that it is Wilber's Cool Structured perspective that informs his categorisation of Jung as an elevationist. I try to demonstrate that Jung's psychic model of the conjunction of opposites is a Hot Structured one, which provides an alternative, soteriological path for persons whose spiritual needs are different from those addressed by Wilber
Oral history interview with Ken Hada
No full textKen Hada, author and professor, talks about his upbringing as a minister's son and shares how he became interested in writing and in poetry. He recalls submitting his first two poems for publication and having them accepted. Hada explains his creative process, the challenge of self-identifying as a writer, and co-founding the Scissortail Creative Writing Festival in Ada, Oklahoma. He also discusses a few of his projects, including writing vignettes to go along with his brother's paintings of the Arkansas River and his book Bring an Extry Mule.The Deep Roots: Oklahoma Authors Collection is a series of interviews with authors who discuss their lives, work, and creative processes
Ken Knight
No full textPhotograph - Ken Knight at Nancy Appleby's home, Christmas 1986. Athabasca, Albert
Career Spotlight: Ken Abdo, Esq.
No full textAn interview with Ken Abdo. He is a partner at the law firm of Fox Rothschild LLP. Spanning forty years, he has extensive experience serving as legal counsel to artists, creators, and businesses in the music and entertainment industries. He is a prolific author and lecturer on music and entertainment law matters. Harnessing his earlier years of experience as a musician, entertainer, and adjunct professor of entertainment law, Ken’s career has been a storied ride working with developing, established, legacy, and estates of music artists. He now represents both buyers and sellers of music artist recording and publishing catalogs. His commitment to advocacy has vaulted him to national and international leadership positions with The Recording Academy, the American Bar Association, The International Association of Entertainment Lawyers, and other organizations
Interview with "The Sun and the Shadow" author, Ken Kelzer
No full textKen Kelzer is a licensed clinical social worker in private practice in Novato, California. He is the author of the recently released autobiographical book The Sun and the Shadow: My Experiment with Lucid Dreamingpublished by A.R.E. Press and available from Lucidity Association
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