Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

Background: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. Methods: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. Results: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin–creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. Conclusion: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.

Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.

Progressive renal impairment (diabetic kidney disease (DKD)) occurs in upwards of 40 % of patients with obesity and type 2 diabetes mellitus (T2DM) and is a cause of significant morbidity and mortality. Means of attenuating the progression of DKD focus on amelioration of risk factors. Visceral obesity is implicated as a causative agent in impaired metabolic and cardiovascular control in T2DM, and various approaches primarily targeting weight have been examined for their impact on markers of renal injury and dysfunction in DKD. The current report summarises the evidence base for the impact of surgical, lifestyle and pharmacological approaches to weight loss on renal end points in DKD. The potential for a threshold of weight loss more readily achievable by surgical intervention to be a prerequisite for renal improvement is highlighted. Comparing efficacious non-surgical weight loss strategies with surgical strategies in appropriately powered and controlled prospective studies is a priority for the field.