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271.
Ryan R. Reisinger Stuart Corney Ben Raymond Amanda T. Lombard Marthn N. Bester Robert J. M. Crawford Delia Davies P. J. Nico de Bruyn Ben J. Dilley Stephen P. Kirkman Azwianewi B. Makhado Peter G. Ryan Stefan Schoombie Kim L. Stevens Cheryl A. Tosh Mia Wege T. Otto Whitehead Michael D. Sumner Simon Wotherspoon Ari S. Friedlaender Cedric Cott Mark A. Hindell Yan Ropert-Coudert Pierre A. Pistorius 《Diversity & distributions》2022,28(1):142-159
272.
Ryan R. Reisinger Stuart Corney Ben Raymond Amanda T. Lombard Marthn N. Bester Robert J. M. Crawford Delia Davies P. J. Nico de Bruyn Ben J. Dilley Stephen P. Kirkman Azwianewi B. Makhado Peter G. Ryan Stefan Schoombie Kim L. Stevens Cheryl A. Tosh Mia Wege T. Otto Whitehead Michael D. Sumner Simon Wotherspoon Ari S. Friedlaender Cedric Cott Mark A. Hindell Yan Ropert-Coudert Pierre A. Pistorius 《Diversity & distributions》2022,28(1):i-i
273.
Neuroblastomas (NBL) and Ewing’s sarcomas (EWS) together cause 18% of all pediatric cancer deaths. Though there is growing interest in targeting the dysregulated metabolism of cancer as a therapeutic strategy, this approach has not been fully examined in NBL and EWS. In this study, we first tested a panel of metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) as the most potent chemotherapeutic across all NBL and EWS cell lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in both of these pediatric malignancies and recent studies have established that Myc causes cancer cells to become “addicted” to glutamine. We found DON strongly inhibited tumor growth of multiple tumor lines in mouse xenograft models. In vitro, inhibition of caspases partially reversed the effects of DON in high Myc expressing cell lines, but not in low Myc expressing lines. We further showed that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro-apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination with the Bcl-2 family antagonist navitoclax (ABT-263). In vitro, this combination caused an increase in DON activity across the entire panel of cell lines tested, with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines. Our study supports targeting glutamine metabolism to treat Myc overexpressing cancers, such as NBL and EWS, particularly in combination with Bcl-2 family antagonists. 相似文献
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Sarah Voisin Kirsten Seale Macsue Jacques Shanie Landen Nicholas R. Harvey Larisa M. Haupt Lyn R. Griffiths Kevin J. Ashton Vernon G. Coffey Jamie-Lee M. Thompson Thomas M. Doering Malene E. Lindholm Colum Walsh Gareth Davison Rachelle Irwin Catherine McBride Ola Hansson Olof Asplund Aino E. Heikkinen Päivi Piirilä Kirsi H. Pietiläinen Miina Ollikainen Sara Blocquiaux Martine Thomis Dawn K. Coletta Adam P. Sharples Nir Eynon 《Aging cell》2024,23(1):e13859
277.
In this study, the mechanism of ischaemia-induced increased sarcolemmal permeability, as manifested by release of intracellular enzymes, was investigated. The role of changes in the sarcolemmal phospholipid bilayer in this process was evaluated by experimental modulation of the phospholipid fatty acid composition. The isolated perfused rat heart subjected to low-flow hypoxia, was used as a model of global ischaemia. Glucose as well as saturated (palmitate) and unsaturated (linoleate) long-chain fatty acids were used as substrates. Hearts perfused with palmitate or linoleate (1.5 mM, fatty acid/albumin ratio, 3.4) showed a significantly higher rate of lactate dehydrogenase release in both control and ischaemic conditions than hearts perfused with glucose (10 mM). Lactate dehydrogenase release in the fatty acid-perfused hearts was associated with a significant increase in the percentage unsaturation of the sarcolemmal phospholipid fatty acids. Glucose-perfused hearts, on the other hand, showed only minor changes in the sarcolemmal phospholipid fatty acid composition. Attempts to correlate enzyme release directly with an increase in the percentage unsaturation of phospholipid fatty acids failed, since enzyme release was also stimulated in control fatty-acid-perfused hearts which (when compared with glucose) contained a higher percentage saturated phospholipid fatty acids. The results suggest that myocardial ischaemia, apart from changes in the sarcolemmal phospholipid fatty acid composition, also induces several other changes in sarcolemmal composition (e.g., cholesterol loss) which may affect is permeability for macromolecules. 相似文献
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M. N. Bester 《Journal of Zoology》1982,196(2):217-231
The present study was undertaken during the summers of 1974/75 and 1975/76. Beaches were classified according to their topography and structure, and colony types were classified according to age and sex composition during the breeding season peak haul-out. Breeding success was measured by the total number of pups born. All available beaches were occupied during the breeding season, breeders predominating on the windward west coast and nonbreeders on the leeward east coast. Principal factors influencing the distribution of breeding fur seals were the topography and physical nature of the beaches, ambient temperatures and solar radiation, sea condition, and exposure to wind and sea spray. The resultant distribution pattern is ascribed to a behavioural thermoregulatory response in A. tropicalis so as to reduce exogenous heat-loading during the summer breeding season. 相似文献