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An extracellular vesicle based hypothesis for the genesis of the polycystic kidney diseases.

Extracell Vesicle

December 2024

The Jared Grantham Kidney Institute at the University of Kansas Medical Center, Department of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Autosomal dominant polycystic kidney (ADPKD) disease is the commonest genetic cause of kidney failure (affecting 1:800 individuals) and is due to heterozygous germline mutations in either of two genes, and . Homozygous germline mutations in are responsible for autosomal recessive polycystic kidney (ARPKD) disease a rare (1:20,000) but severe neonatal disease. The products of these three genes, (polycystin-1 (PC1 4302(3)aa)), (polycystin-2 (PC2 968aa)) and (fibrocystin (4074aa)) are all present on extracellular vesicles (EVs) termed, PKD-exosome-like vesicles (PKD-ELVs).

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Advances in the detection and treatment of cancer have translated into improved cancer survival rates and a growing population of cancer survivors. These include those living with cancer and individuals free of the disease following treatment. Epidemiological studies demonstrate that cancer survivors are at an increased risk of cardiovascular disease (CVD), with cardiovascular (CV) mortality overtaking cancer mortality in some tumour types.

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Objectives: Assessment of age, sex and smoking-specific risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms.

Methods And Analysis: Data on patients aged 30-99 in 2007-2017 were extracted from a UK primary care database (CPRD Gold), comprising a randomly selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump and post-menopausal bleed).Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality and to estimate cumulative incidence up to 12 months following index consultation.

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Objective: Inducing tumour cell apoptosis is a primary objective of chemotherapy but, to date, there are no validated biomarkers of apoptosis sensitivity or resistance. Our objective was to image multiple apoptosis pathway proteins at single cell level and determine multi-protein associations with recurrence risk and chemotherapy response in patients with stage II colorectal cancer (CRC).

Methods And Analysis: Multiplexed imaging of 16 proteins in the intrinsic and extrinsic apoptosis pathways at single cell resolution on resected tissue from 194 patients with stage II CRC who either received adjuvant chemotherapy (n108) or were treated with surgery only (n=86).

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Aims: Cardiac arrest is registered in the Danish National Patient Registry (DNPR) with the International Classification of Diseases 10 revision code I46. However, it does not distinguish between out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We validated an algorithm to identify cardiac arrest subtypes (out-of-hospital vs.

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