Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year ...survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.
Display omitted
•Non-tumor tissue seems to have higher antioxidant capacity than tumor tissue.•Antioxidant enzymes are higher in stage II than stage I in tumor and non-tumor tissue.•Antioxidant ...enzymes may become important biomarkers of early stages of CRC.
Antioxidant defences and oxidative stress are related to development, progression and malignancy of colorectal cancer. However, their role in early stages of cancer remains unknown. More and more recent studies have revealed that non-tumour adjacent tissue is not a normal tissue. Thus, our aim was to analyse protein levels of MnSOD (Manganese Superoxide Dismutase), acMnSOD (Acetylated Manganese superoxide Dismutase), SIRT3 (Sirtuin 3), CuZnSOD (Cupper Zinc Superoxide Dismutase), CAT (Catalase), GPx (Glutathione Peroxidase), and GRd (Glutathione Reductase) both in tumour and non-tumour adjacent tissue from colorectal cancer patients by western blot. Non-tumour adjacent tissue seemed to have higher levels of antioxidant enzymes that detoxify hydrogen peroxide compared to tumour tissue. In contrast, tumour tissue had higher levels of MnSOD and acMnSOD. Furthermore, most of the proteins analysed showed significant differences between stage I and II in both non-tumour adjacent and tumour tissue. This could indicate that antioxidant enzymes, especially MnSOD, play a crucial role in early stages of colorectal cancer in both tissues, so they could be analysed as novel biomarkers to improve colorectal cancer diagnosis.
Alkylphospholipids (APLs) have been studied as anticancer drugs that interfere with biological membranes without targeting DNA. Although their mechanism of action is not fully elucidated yet, it is ...known that they disrupt the intracellular trafficking of cholesterol and its metabolism. Here, we analyzed whether APLs could also interfere with mitochondrial function. For this purpose, we used HT29 colorectal cancer cells, derived from a primary tumor, and SW620 colorectal cancer cells, derived from a metastasis site. After treatment with the APLs miltefosine and perifosine, we analyzed various mitochondrial parameters, including mitochondrial mass, cardiolipin content, mitochondrial membrane potential, H
O
production, the levels of oxidative phosphorylation (OXPHOS) complexes, metabolic enzymes activity, the oxygen consumption rate, and the levels of apoptosis and autophagy markers. APLs, especially perifosine, increased mitochondrial mass while OXPHOS complexes levels were decreased without affecting the total oxygen consumption rate. Additionally, we observed an increase in pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) levels and a decrease in lactate dehydrogenase (LDH) activity, suggesting a metabolic rewiring induced by perifosine. These alterations led to higher mitochondrial membrane potential, which was potentiated by decreased uncoupling protein 2 (UCP2) levels and increased reactive oxygen species (ROS) production. Consequently, perifosine induced an imbalance in mitochondrial function, resulting in higher ROS production that ultimately impacted cellular viability.
Most colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations ...associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whether they could ultimately be used as a therapeutic target in metastatic colorectal cancer (mCRC). We analyzed the protein levels by Western blotting and the enzymatic activities of proteins involved in mitochondrial function, as well as the amount of mitochondrial DNA (mtDNA), by real-time PCR, analyzing samples of non-tumor adjacent tissue and tumor tissue from stages III and IV CRC patients without radio- or chemotherapy treatment prior to surgery. Our data indicate that the tumor tissue of pre-metastatic stage III CRC exhibited an oxidant metabolic profile very similar to the samples of non-tumor adjacent tissue of both stages. Notable differences in the protein expression levels of ATPase, IDH2, LDHA, and SIRT1, as well as mtDNA amount, were detected between the samples of non-tumor adjacent tissue and tumor tissue from metastatic CRC patients. These findings suggest a shift in the oxidative metabolic profile that takes place in the tumor tissue once the metastatic stage has been reached. Tumor tissue oxidative metabolism contributes to promote and maintain the metastatic phenotype, with evidence of mitochondrial function impairment in stage IV tumor tissue.
Abstract
Background
The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction ...while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. The objective of the study is to evaluate previously to the implementation whether the benefits of introducing ultrasound-guided peripheral venous catheters, midline catheters and peripherally inserted central catheters compared to current practice by a vascular access specialist team outweigh their costs.
Methods
Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when changing the current practice for the use of ultrasound-guided midline and PICC catheters, as well as the additional resources required for their use.
Results
The use of an ultrasound-guided device on peripherally inserted central carheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, the use of an ultrasound-guided device on a midline catheter, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96.
Conclusion
The benefits of using ultrasound-guided midline and PICC catheters compared to current practice by introducing a vascular access specialist team trained in the implantation of ultrasound-guided catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of phebitis. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.
Xanthohumol (XN) is a prenylated flavonoid known for its antioxidant and anti-inflammatory effects and has been studied as an anti-cancer agent. In this study, we aimed at analysing the effect of XN ...on a primary colorectal adenocarcinoma cell line, HT29, on cell viability, inflammatory and antioxidant gene expression, and metabolism. For this purpose, cells were treated with 10 nM and 10 µM XN, and cell viability, H
2
O
2
production, lipid peroxidation and gene expression of inflammatory, antioxidant, and mitochondrial-related genes, as well as protein levels of metabolic enzymes, were determined. Results showed no significant effects on cell viability and a general decrease in pro-inflammatory, antioxidant and mitochondrial biogenesis gene expression with the lower concentration of XN. Furthermore, glucose and oxidative metabolism enzymes were also reduced. These results suggest that XN treatment, at low doses, could stop the proliferation and progression of HT29 cells by downregulating inflammatory signals and cell metabolism.
Abstract Background There is no proven pharmacological strategy for the treatment of the failing systemic right ventricle (SRV) but myocardial fibrosis may play a role in its pathophysiology. Methods ...We designed a double-blind, placebo-controlled clinical trial to assess the effects of eplerenone 50 mg during 12 months on cardiac magnetic resonance parameters (SRV mass and ejection fraction) and neurohormonal and collagen turnover biomarker (CTB) levels. Results Twenty six patients with atrial switch repair for transposition of the great arteries were randomized to eplerenone (n = 14) or placebo (n = 12) and 14 healthy volunteers served as controls for comparison of baseline neurohormones and CTB levels. The study population showed a good baseline profile in terms of SRV mass (57.4 ± 17 g/m2 ) and ejection fraction (54.9 ± 7.5%). However, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), C terminal propeptide of type I procollagen (CICP) and C-terminal Telopeptide of type I Collagen (ICTP) were significantly elevated when compared to healthy controls. After one year of treatment, a trend toward reduction of CICP, N-terminal pro-Matrix Metalloproteinase 1 (NT-proMMP1), Tissue Inhibitor of Metalloproteinases 1 (TIMP1) and galectin 3 levels and a lower increase in ICTP in patients under eplerenone was observed. The reduction of SRV mass and the improvement of SRV function with eplerenone were not conclusive. Conclusions Patients with SRV treated with eplerenone showed an improvement of an altered baseline CTB profile suggesting that reduction of myocardial fibrosis might be a therapeutic target in these patients.
The evaluation of integrated care programmes for
older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in ...Catalonia, Spain.
We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay.
264 cases were included (91% at home; 9% in nursing homes). 6-month pre vs. 6-months post results were (mean, p-value): primary care visits 8.2 vs. 11.5 (p < 0.05); emergency department visits 1.4 vs. 0.9 (p < 0.05); hospital admissions 0.7 vs. 0.5 (p < 0.05); hospital stay 12.8 vs. 7.9 days (p < 0.05). Time spent at home was 169.2 vs.174.2 days (p < 0.05).
Early implementation of the ProPCC programme results in an increase in time spent at home (up to 3%) and significant reductions in emergency department attendance (-37.2%) and hospital stays (-38.3%). The increased use of primary care resources is compensated by the hospital resources savings, with a result in the average total cost of -46.3%.
Colorectal cancer (CRC) is a leading cause of malignant cancer-related morbidity and mortality, with a higher incidence in developed countries and a high mortality rate mainly attributable to ...metastases. The aim of the present study was to determine the metabolic adaptations related to oxidative stress in tumor tissue from advanced stages (III and IV) of CRC and whether they could be used as potential biomarkers for clinical applications. To tackle this aim, we have analyzed the protein expression levels related to oxidative stress and the enzymatic activities of MnSOD and catalase, comparing samples of non-tumor adjacent tissue and tumor tissue of CRC patients in stages III and IV. The results showed no differences between stage III and IV in tumor tissues for any of the proteins studied. However, some differences were found between samples of non-tumor adjacent tissue and tumor tissue for some of the antioxidant enzymes. Overwhelmingly, the greatest differences were detected when comparing samples of non-tumor adjacent tissue from stage III and stage IV. To the best of our knowledge, this is the first study where differences between the non-tumor adjacent tissues of CRC patients from different cancer stages were determined. This study suggests that the parameters analyzed should be evaluated as biomarkers for the evolution of CRC. Furthermore, tumor tissue status should not be of sole importance for the prognosis of CRC, as the non-tumor adjacent tissues could also merit consideration.
Display omitted
•Differences between non-tumor adjacent tissues of CRC in stages III vs IV are shown.•CRC stage IV non-tumor adjacent tissue shows higher activated antioxidant response than in stage III.•Changes in non-tumor adjacent tissue could be evaluated as a CRC biomarkers source.
PDF
