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Full-Text Articles in Cancer Biology
Investigation Of Zyflamend On Ampk Signaling And Potential Interactions Of Its Components, Yi Zhao
Investigation Of Zyflamend On Ampk Signaling And Potential Interactions Of Its Components, Yi Zhao
Doctoral Dissertations
The reductionist approach contributes greatly to our understanding of anticancer properties of phytonutrients, but in vitro studies demand concentrations that are 100-1000 times higher than achievable in humans, producing results with little physiologic relevance, resulting in disappointing outcomes in clinical trials. However, maintaining these bioactives in the presence of other compounds originally derived from the food/extract of origin may synergistically lower the bioactive dose so translatability becomes feasible. The first objective of this study was to determine if bioefficacy of phytonutrients can be enhanced when used in combination at doses that are ineffective when used in isolation. In this project, …
Rheb Dynamics On Lysosomal Membranes Determines Mtorc1 Activity After Loss Of P53 Or Activation Of Ampk, Catherine M. Bell
Rheb Dynamics On Lysosomal Membranes Determines Mtorc1 Activity After Loss Of P53 Or Activation Of Ampk, Catherine M. Bell
Theses and Dissertations
The tumor suppressor TP53 is the most frequently altered gene in human cancers. The growth-promoting complex, mTORC1 plays a part of the oncogenic profile caused by dysfunctional p53. mTORC1 sits downstream of AMPK and other crucial tumor suppressors/oncogenes, PTEN, LKB1, and Akt. The antifolate pemetrexed was found by this laboratory to activate AMPK via the inhibition of the enzyme AICART in de novo purine synthesis. This work presents a mechanism of mTORC1 activation with p53 loss, as well as of mTORC1 inhibition by pemetrexed-induced AMPK. We have found that mTORC1 activity was substantially upregulated by the loss …
Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal
Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal
Theses and Dissertations
New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …