Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

<p>Abstract</p> <p>Background</p> <p>Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease.</p> <p>Methods</p> <p>Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples.</p> <p>Results</p> <p>Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component.</p> <p>Conclusion</p> <p>We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue.</p

Design of a factorial experiment with randomization restrictions to assess medical device performance on vascular tissue

Background: Energy-based surgical scalpels are designed to efficiently transect and seal blood vessels using thermal energy to promote protein denaturation and coagulation. Assessment and design improvement of ultrasonic scalpel performance relies on both in vivo and ex vivo testing. The objective of this work was to design and implement a robust, experimental test matrix with randomization restrictions and predictive statistical power, which allowed for identification of those experimental variables that may affect the quality of the seal obtained ex vivo. Methods: The design of the experiment included three factors: temperature (two levels); the type of solution used to perfuse the artery during transection (three types); and artery type (two types) resulting in a total of twelve possible treatment combinations. Burst pressures of porcine carotid and renal arteries sealed ex vivo were assigned as the response variable. Results: The experimental test matrix was designed and carried out as a split-plot experiment in order to assess the contributions of several variables and their interactions while accounting for randomization restrictions present in the experimental setup. The statistical software package SAS was utilized and PROC MIXED was used to account for the randomization restrictions in the split-plot design. The combination of temperature, solution, and vessel type had a statistically significant impact on seal quality. Conclusions: The design and implementation of a split-plot experimental test-matrix provided a mechanism for addressing the existing technical randomization restrictions of ex vivo ultrasonic scalpel performance testing, while preserving the ability to examine the potential effects of independent factors or variables. This method for generating the experimental design and the statistical analyses of the resulting data are adaptable to a wide variety of experimental problems involving large-scale tissue-based studies of medical or experimental device efficacy and performance

Systematic Reviews and Meta-Analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery

\ua9 2024 Lippincott Williams and Wilkins. All rights reserved.Objective: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. Background: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. Methods: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. Results: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of &lt;0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. Conclusions: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding

Development of a Surface Plasmon Resonance Biosensor for Real-Time Detection of Osteogenic Differentiation in Live Mesenchymal Stem Cells

Surface plasmon resonance (SPR) biosensors have been recognized as a useful tool and widely used for real-time dynamic analysis of molecular binding affinity because of its high sensitivity to the change of the refractive index of tested objects. The conventional methods in molecular biology to evaluate cell differentiation require cell lysis or fixation, which make investigation in live cells difficult. In addition, a certain amount of cells are needed in order to obtain adequate protein or messenger ribonucleic acid for various assays. To overcome this limitation, we developed a unique SPR-based biosensing apparatus for real-time detection of cell differentiation in live cells according to the differences of optical properties of the cell surface caused by specific antigen-antibody binding. In this study, we reported the application of this SPR-based system to evaluate the osteogenic differentiation of mesenchymal stem cells (MSCs). OB-cadherin expression, which is up-regulated during osteogenic differentiation, was targeted under our SPR system by conjugating antibodies against OB-cadherin on the surface of the object. A linear relationship between the duration of osteogenic induction and the difference in refractive angle shift with very high correlation coefficient was observed. To sum up, the SPR system and the protocol reported in this study can rapidly and accurately define osteogenic maturation of MSCs in a live cell and label-free manner with no need of cell breakage. This SPR biosensor will facilitate future advances in a vast array of fields in biomedical research and medical diagnosis

Temporal patterns and trends of particulate matter over Portugal: a long-term analysis of background concentrations

Air quality management regarding PM concentrations in the atmosphere is a complex problem to tackle. In this paper, we aim to characterize the temporal patterns and trends of aerosol background levels over Portugal. Hourly data from the national air quality monitoring network, gathered from 2007 to 2016, is analyzed using statistical methods. Data from 20 monitoring stations was processed to prepare datasets with different time scales, and results were grouped by their type of surrounding area (urban, suburban, or rural). Urban and suburban background sites are characterized by strong seasonal patterns, with higher monthly mean concentrations in winter than in summer. In contrast, rural background PM10 concentrations are highest during August and September. This study suggests that urban background concentrations are significantly influenced by anthropogenic non-combustion sources, which contribute to the coarser aerosol fraction (PMc). PMc is about 3 μg m−3 higher during weekdays than during Sundays, at urban sites. However, there is no clear relationship between the value of the PM2.5/PMc ratio and the type of monitoring station. During the 10-year period of study, a decrease of 1.83, 3.58, and 4.89%/year was registered in PM10 concentrations at Portuguese rural, urban, and suburban areas, respectively. Despite the higher decrease at suburban monitoring stations, those sites present the highest 10-year mean PM10 concentrations. This work provides an import insight on temporal variations of PM10, PM2.5, and PMc concentrations over Portugal and summarizes trends through the last decade, contributing to the discussion on sources and processes influencing those concentrations.Thanks also are due to the Portuguese Agency for the Environment (APA) and the Regional Coordination and Development Commissions (CCDRs) for their effort in establishing and maintaining the air quality monitoring sites used in this investigation.publishe

Plant defences mediate interactions between herbivory and the direct foliar uptake of atmospheric reactive nitrogen

Reactive nitrogen from human sources (e.g., nitrogen dioxide, NO2) is taken up by plant roots following deposition to soils, but can also be assimilated by leaves directly from the atmosphere. Leaf uptake should alter plant metabolism and overall nitrogen balance and indirectly influence plant consumers; however, these consequences remain poorly understood. Here we show that direct foliar assimilation of NO2 increases levels of nitrogen-based defensive metabolites in leaves and reduces herbivore consumption and growth. These results suggest that atmospheric reactive nitrogen could have cascading negative effects on communities of herbivorous insects. We further show that herbivory induces a decrease in foliar uptake, indicating that consumers could limit the ability of vegetation to act as a sink for nitrogen pollutants (e.g., smog from mobile emissions). Our study suggests that the interactions of foliar uptake, plant defence and herbivory could have significant implications for understanding the environmental consequences of reactive nitrogen