
Gregory Naylor- University of Glasgow
Gregory Naylor
- University of Glasgow
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10
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Publications (10)
Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas d...
Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas d...
The morphological changes during apoptosis help facilitate “immunologically silent” cell death. Caspase cleavage of the ROCK1 kinase results in its activation, which drives the forceful contraction of apoptotic cells. We previously showed that when ROCK1 was mutated to render it caspase-resistant, there was greater liver damage and neutrophil recru...
3103
Background: CDC7, a protein with key roles in regulating cell-cycle progression is often over-expressed in malignant cells, particularly those with TP53 mutations. LY3143921, an orally administered ATP-competitive CDC7 inhibitor, demonstrated favorable pre-clinical anti-cancer activity in colorectal cancer (CRC) and squamous non-small cell lun...
The characteristic changes in morphology during apoptosis help facilitate "immunologically-silent" cell death by limiting the release of cellular contents and enabling efficient clearance of apoptotic cell bodies. Caspase-mediated cleavage of the ROCK1 protein kinase results in its constitutive activation, which drives the rapid and forceful contra...
390
Background: Sorafenib, lenvatinib and regorafenib have proven efficacy in patients with HCC in randomised clinical trials. First line sorafenib significantly improves overall survival (OS) and disease control rates vs. placebo (SHARP) whilst lenvatinib (REFLECT) is non-inferior to sorafenib in terms of OS. Second line regorafenib improves OS ve...
Apoptosis is characterized by profound morphological changes, but their physiological purpose is unknown. To characterize the role of apoptotic cell contraction, ROCK1 was rendered caspase non-cleavable (ROCK1nc) by mutating Aspartate 1113, which revealed that ROCK1 cleavage was necessary for forceful contraction and membrane blebbing. When homozyg...
93
Background: The fluoropyrimidines (FP), 5-Fluorouracil (5-FU) and capecitabine are a mainstay of colorectal cancer (CRC) treatment. Dihydropyrimidine dehydrogenase (DPYD), an enzyme encoded by the DPYD gene, is the initial and rate-limiting step in pyrimidine catabolism, deactivating over 80% of 5-FU. Approximately 5% of the population are defic...
TPS3167
Background: CDC7 is a protein with key roles in DNA replication initiation, the intra-S-phase checkpoint and M-phase completion. CDC7 is over-expressed in malignant compared to non-malignant cells, particularly those with TP53 mutations, making it an attractive therapeutic target. LY3143921 hydrate is an orally administered ATP-competitive...
The myotonic dystrophy–related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin–myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potenti...