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Full-Text Articles in Medicine and Health Sciences
Recent Advances In Cancer Stem/Progenitor Cell Research: Therapeutic Implications For Overcoming Resistance To The Most Aggressive Cancers., M. Mimeault, Ralph Hauke, Parmender P. Mehta, Surinder K. Batra
Recent Advances In Cancer Stem/Progenitor Cell Research: Therapeutic Implications For Overcoming Resistance To The Most Aggressive Cancers., M. Mimeault, Ralph Hauke, Parmender P. Mehta, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that …
Formation Of Native Prions From Minimal Components In Vitro, Nathan R. Deleault, Brent T. Harris, Judy R. Rees, Surachai Supattapone
Formation Of Native Prions From Minimal Components In Vitro, Nathan R. Deleault, Brent T. Harris, Judy R. Rees, Surachai Supattapone
Dartmouth Scholarship
The conformational change of a host protein, PrPC, into a disease-associated isoform, PrPSc, appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt–Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown. To investigate the mechanism of prion formation biochemically, we conducted a series of experiments using the protein misfolding cyclic amplification (PMCA) technique with a preparation containing only native PrPC and copurified lipid molecules. These experiments showed that successful PMCA propagation of PrPScmolecules in a purified system requires accessory polyanion molecules. In addition, we found that …
P53 Activation By Knockdown Technologies, Mara E. Robu, Jon D. Larson, Aidas Nasevicius, Soraya Beiraghi, Charles Brenner
P53 Activation By Knockdown Technologies, Mara E. Robu, Jon D. Larson, Aidas Nasevicius, Soraya Beiraghi, Charles Brenner
Dartmouth Scholarship
Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short interfering RNAs (siRNAs) are commonly used platforms to study gene function by sequence-specific knockdown. Both technologies, however, can elicit undesirable off-target effects. We have used several model genes to study these effects in detail in the zebrafish, Danio rerio. Using the zebrafish embryo as a template, correct and mistargeting effects are readily discernible through direct comparison of MO-injected animals with well-studied mutants. We show here indistinguishable off-targeting effects for both maternal and zygotic mRNAs and for both translational and splice-site targeting MOs. The major off-targeting effect is mediated through p53 activation, as detected …
The Notch Regulator Maml1 Interacts With P53 And Functions As A Coactivator., Yongtong Zhao, Rebecca B. Katzman, Laurie M. Delmolino, Ishfaq Bhat, Ying Zhang, Channabasavaiah B. Gurumurthy, Aleksandra Germaniuk-Kurowska, Honey V. Reddi, Aharon Solomon, Mu-Sheng Zeng, Aisha Kung, Hui Ma, Qingshen Gao, Goberdhan Dimri, Adina Stanculescu, Lucio Miele, Lizi Wu, James D. Griffin, David E. Wazer, Hamid Band, Vimla Band
The Notch Regulator Maml1 Interacts With P53 And Functions As A Coactivator., Yongtong Zhao, Rebecca B. Katzman, Laurie M. Delmolino, Ishfaq Bhat, Ying Zhang, Channabasavaiah B. Gurumurthy, Aleksandra Germaniuk-Kurowska, Honey V. Reddi, Aharon Solomon, Mu-Sheng Zeng, Aisha Kung, Hui Ma, Qingshen Gao, Goberdhan Dimri, Adina Stanculescu, Lucio Miele, Lizi Wu, James D. Griffin, David E. Wazer, Hamid Band, Vimla Band
Journal Articles: Biochemistry & Molecular Biology
Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that …