ORCID Profile
0000-0003-0225-9211
Current Organisation
University of Ottawa
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Publisher: Wiley
Date: 20-03-2020
Publisher: Portland Press Ltd.
Date: 06-07-2015
DOI: 10.1042/BJ20150122
Abstract: Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in in iduals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK–ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (& .0 mM) effects not observed in prostate (PNT1A) and lung (MRC-5) epithelial cell lines. Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 μM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted.
Publisher: Georg Thieme Verlag KG
Date: 16-03-2021
Abstract: This case highlights a hybrid treatment model used successfully in a patient with complicated recurrent renal cell carcinoma (RCC), following partial nephrectomy, in the context of a single kidney. Scar tissue from previous surgery tethered the ureter to the margin of the lesion and combined with obesity, rendered simple percutaneous intervention challenging. The patient was ultimately successfully treated using a hybrid approach of open surgical access, ureterolysis, and intraoperative ultrasound-guided radiofrequency ablation. This approach optimized the volume of conserved normal renal parenchyma and eliminated the need for postoperative dialysis treatment, with no recurrence at 13 months follow-up.
Publisher: Wiley
Date: 11-07-2023
DOI: 10.1111/AJR.13014
Abstract: Life and limb threatening vascular emergencies often present to rural hospitals where only general surgery services are available. It is known that Australian rural general surgical centres encounter 10–20 emergency vascular surgery procedures annually. This study aimed to assess rural general surgeons' confidence managing emergent vascular procedures. A survey was distributed to Australian rural general surgeons to determine their confidence (Yes/No) in performing emergent vascular procedures including limb revascularisation, revising arterio‐venous (AV) fistulas, open repair of ruptured abdominal aortic aneurysm (AAA), superior mesenteric artery (SMA)/coeliac embolectomy, limb embolectomy, vascular access catheter insertion and limb utation (digit, forefoot, below knee and above knee). Confidence level was compared with surgeon demographics and training. Variables were compared using univariate logistic regression. Sixteen per cent (67/410) of all Australian rural general surgeons responded to the survey. Increased age, years since fellowship and training prior to 1995 (when separation of Australian vascular and general surgery occurred) were associated with greater confidence in limb revascularisation, revising AV fistulas, open repair of ruptured AAA, SMA/coeliac embolectomy, and limb embolectomy ( p 0.05). Surgeons who completed months of vascular surgery training were more comfortable with SMA/coeliac embolectomy (49% vs. 17%, p = 0.01) and limb embolectomy (59% vs. 28%, p = 0.02). Confidence in performing limb utation was similar across surgeon demographics and training ( p 0.05). Recently graduated rural general surgeons do not feel confident in managing vascular emergencies. Additional vascular surgery training should be considered as part of general surgical training and rural general surgical fellowships.
Publisher: Wiley
Date: 03-08-2020
DOI: 10.1002/AJUM.12220
Publisher: Wiley
Date: 03-09-2020
No related grants have been discovered for Andrew O'Brien.