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Full-Text Articles in Medicine and Health Sciences

Therapeutic Targeting Of Replicative Immortality, Paul Yaswen, Karen L. Mackenzie, W. Nicol Keith, Patricia Hentosh, Francis Rodier, Jiyue Zhu, Gary L. Firestone, Ander Matheu, Amancio Carnero, Alan Bilsland Jan 2015

Therapeutic Targeting Of Replicative Immortality, Paul Yaswen, Karen L. Mackenzie, W. Nicol Keith, Patricia Hentosh, Francis Rodier, Jiyue Zhu, Gary L. Firestone, Ander Matheu, Amancio Carnero, Alan Bilsland

Medical Diagnostics & Translational Sciences Faculty Publications

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite …


Designing A Broad-Spectrum Integrative Approach For Cancer Prevention And Treatment, Keith I. Block, Charlotte Gyllenhaal, Leroy Lowe, Amedeo Amedei, A.R.M. Ruhul Amin, Amr Amin, Katia Aquilano, Jack Arbiser, Alexandra Arreola, Alla Arzumanyan, Patricia Hentosh Jan 2015

Designing A Broad-Spectrum Integrative Approach For Cancer Prevention And Treatment, Keith I. Block, Charlotte Gyllenhaal, Leroy Lowe, Amedeo Amedei, A.R.M. Ruhul Amin, Amr Amin, Katia Aquilano, Jack Arbiser, Alexandra Arreola, Alla Arzumanyan, Patricia Hentosh

Medical Diagnostics & Translational Sciences Faculty Publications

Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic …


Bioactive Lipid Coating Of Bone Allografts Direct Engraftment And Fate Determination Of Bone Marrow-Derived Cells In Rat Gfp Chimeras, Anusuya Das, Claire E. Segar, Yihsuan Chu, Tiffany W. Wang, Yon Lin, Chunxi Yang, Roy C. Ogle Jan 2015

Bioactive Lipid Coating Of Bone Allografts Direct Engraftment And Fate Determination Of Bone Marrow-Derived Cells In Rat Gfp Chimeras, Anusuya Das, Claire E. Segar, Yihsuan Chu, Tiffany W. Wang, Yon Lin, Chunxi Yang, Roy C. Ogle

Medical Diagnostics & Translational Sciences Faculty Publications

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both …