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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman
Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman
Dartmouth Scholarship
Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.
Serine/Threonine Kinase 17a Is A Novel Candidate For Therapeutic Targeting In Glioblastoma, Pingping Mao, Mary P. Hever-Jardine, Gilbert J. Rahme, Eric Yang, Janice Tam, Anita Kodali, Bijesh Biswal, Camilo E. Fadul, Arti Gaur, Mark A. Israel, Michael J. Spinella
Serine/Threonine Kinase 17a Is A Novel Candidate For Therapeutic Targeting In Glioblastoma, Pingping Mao, Mary P. Hever-Jardine, Gilbert J. Rahme, Eric Yang, Janice Tam, Anita Kodali, Bijesh Biswal, Camilo E. Fadul, Arti Gaur, Mark A. Israel, Michael J. Spinella
Dartmouth Scholarship
STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents in a p53-dependent manner. In this study we have uncovered an additional, unanticipated role for STK17A as a candidate promoter of cell proliferation and survival in glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly overexpressed in a grade-dependent manner in gliomas compared to normal brain and other cancer cell types with the …
Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari
Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari
Dartmouth Scholarship
One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using …
Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan
Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan
Dartmouth Scholarship
Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …
Evidence For Tankyrases As Antineoplastic Targets In Lung Cancer, Alexander M. Busch, Kevin C. Johnson, Radu V. Stan, Aarti Sanglikar, Yashi Ahmed, Ethan Dmitrovsky, Sarah J. Freemantle
Evidence For Tankyrases As Antineoplastic Targets In Lung Cancer, Alexander M. Busch, Kevin C. Johnson, Radu V. Stan, Aarti Sanglikar, Yashi Ahmed, Ethan Dmitrovsky, Sarah J. Freemantle
Dartmouth Scholarship
Background: New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β -catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β -catenin phosphorylation complex. Methods: This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and …
Fluorescent Affibody Peptide Penetration In Glioma Margin Is Superior To Full Antibody, Kristian Sexton, Kenneth Tichauer, Kimberley S. Samkoe, Jason Gunn, P. Jack Hoopes, Brian W. Pogue
Fluorescent Affibody Peptide Penetration In Glioma Margin Is Superior To Full Antibody, Kristian Sexton, Kenneth Tichauer, Kimberley S. Samkoe, Jason Gunn, P. Jack Hoopes, Brian W. Pogue
Dartmouth Scholarship
Object: Fluorescence imaging has the potential to significantly improve neurosurgical resection of oncologic lesions through improved differentiation between normal and cancerous tissue at the tumor margins. In order to successfully mark glioma tissue a fluorescent tracer must have the ability to penetrate through the blood brain barrier (BBB) and provide delineation in the tumor periphery where heterogeneously intact BBB may exist. In this study it was hypothesized that, due to its smaller size, fluorescently labeled anti-EGFR Affibody protein (~7 kDa) would provide a more clear delineation of the tumor margin than would fluorescently labeled cetuximab, a full antibody (~150 kDa) …
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Dartmouth Scholarship
There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.
Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo
Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo
Dartmouth Scholarship
During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here …
Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev
Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev
Dartmouth Scholarship
The proteasome inhibitor bortezomib (Velcade) is prescribed for the treatment of multiple myeloma. Clinically achievable concentrations of bortezomib cause less than 85% inhibition of the chymotrypsin-like activity of the proteasome, but little attention has been paid as to whether in vitro studies are representative of this level of inhibition. Patients receive bortezomib as an intravenous or subcutaneous bolus injection, resulting in maximum proteasome inhibition within one hour followed by a gradual recovery of activity. In contrast, most in vitro studies use continuous treatment so that activity never recovers. Replacing continuous treatment with 1 h-pulse treatment increases differences in sensitivity in …
Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson
Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson
Dartmouth Scholarship
Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …