69 research outputs found
Detection od MicroRNAs in archival cytology urine smears
No full textMicroRNAs' dysregulation and profiling have been demonstrated to be clinically relevant in urothelial carcinoma (UC). Urine cytology is commonly used as the mainstay non-invasive test for secondary prevention and follow-up of UC patients. Ancillary tools are needed to support cytopathologists in the diagnosis of low-grade UC. The feasibility and reliability of microRNAs profiling by qRT-PCR analysis (miR-145 and miR-205) in archival routine urine cytology smears (affected by fixation/staining [Papanicolau] and room temperature storage) was tested in a series of 15 non-neoplastic and 10 UC urine specimens. Only samples with >5,000 urothelial cells and with <50% of inflammatory cells/red blood cells clusters were considered. Overall, a satisfactory amount of total RNA was obtained from all the considered samples (mean 1.27±1.43 μg, range 0.06-4.60 μg). Twenty nanograms of total RNA have been calculated to be the minimal total RNA concentration for reliable and reproducible miRNAs expression profiling analysis of archival cytological smears (slope= -3.4084; R-squared=0.99; efficiency=1.94). miR-145 and miR-205 were significantly downregulated in UC samples in comparison to non-tumor controls. These findings demonstrate that urine archival cytology smears are suitable for obtaining high-quality RNA to be used in microRNAs expression profiling. Further studies should investigate if miRNAs profiling can be successfully translated into clinical practice as diagnostic or prognostic markers
Global blood gene expression profiles following a breast cancer diagnosis - Clinical follow-up in the NOWAC post-genome cohort
No full textObjective - This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease.
Material and methods - A random distribution of follow-up time from breast cancer diagnosis till blood sampling was obtained by a nested, matched case-control design in the Norwegian Women and Cancer Post-genome Cohort. From 2002–5, women were invited to donate blood samples, regardless of any cancer diagnosis. At end of the study period in 2015, any cancer diagnoses in the 50 000 participants were obtained via linkage to the Norwegian Cancer Registry. For each breast cancer patient (n = 415), an age- and storage time-matched control was drawn. The design gave a uniform, random length of follow-up time, independent of cancer stage. Differences in blood gene expression between breast cancer cases and controls were identified using the Bioconductor R-package limma, using a moving window in time, to handle the varying time elapsed from diagnosis to blood sample.
Results - The number of differentially expressed genes between cases and controls were close to 2,000 in the first year after diagnosis, but fell sharply the second year. During the next years, a transient second increase was observed, but only in women with metastatic disease who later died, both compared to invasive cases that survived (p
Conclusion - This explorative analysis identified changing trajectories in the years after diagnosis, depending on clinical stage. Hypothetically, this could represent the escape of the metastatic cancer from the immune system
Fatal myocardial depression and circulatory collapse associated with complement activation induced by plasma infusion in severe porcine sepsis
No full textPlasma Therapies in Thrombotic Syndromes
No full textBackground Plasma therapies are being applied to thombotic syndromes, but there are limited controlled studies. Objective To review the evidence and the current practices for plasma therapies in thrombotic syndromes. Methods Expert-enhanced evidence-based analysis. Evidence obtained as of Dec 31, 2002 using Pub Med electronic reference library and expert-obtained library for a total of > 3,000 references obtained using the terms plasma therapy or plasma exchange or plasmapheresis or plasmafiltration or sorbents each combined with the words thrombotic syndrome or sepsis or septic shock. The authors screened the abstracts, reviewed the agreed set of papers, and compiled the recommendations. Results Plasma therapies, which alter the plasma components in patients, have been applied in thrombotic syndromes worldwide. In these patients, there is a biologic plausibility for plasma therapies since they have molecules that are prothrombotic and/or antifibrinolytic which would put them at risk for microvascular thrombosis and end-organ damage. There are respectively one randomized controlled trial (RCT) in primary thrombotic syndrome, and secondary thrombotic syndrome, which showed an improvement in mortality in applying plasma therapies (plasma exchange by centrifugation). However, there are numerous non-randomized and case series. Plasma exchange is accepted as the standard therapy for primary thrombotic syndrome as in thrombotic thrombocytopenic purpura (TTP). However, no consensus has been reached for plasma exchange in secondary thrombotic syndromes such as in sepsis, hemolytic uremic syndrome (HUS), thrombocytopenia associated multiple organ failure, TTP/HUS, s/p bone marrow or solid organ transplant, HELLP syndrome, immunologic disorders, drug exposure, or pancreatitis. Conclusions As we understand more about the pathophysiology of thrombotic syndromes, specific plasma therapies can be applied for the specific need of a particular patient population. There are sufficient preliminary data to recommend a definitive RCT to evaluate the efficacy of the different types of plasma therapies in secondary thrombotic syndromes. </jats:sec
The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma
No full textAims: Macrophage colony-stimulating factor (M-CSF) binds to colony-stimulating factor-1 receptor (CSF-1R) and stimulates proliferation and differentiation of monocytes, macrophages and their bone marrow progenitors. M-CSF, CSF-1R, the macrophage marker CD68, and the pan T-lymphocyte marker CD3 are increased in many human cancers. Their prognostic importance in primary prostatic carcinoma has not been fully delineated. The aim was to compare the expression of M-CSF, CSF-1R, CD68 and CD3 in metastatic and non-metastatic prostatic cancer. Methods and results: Digital video analysis of tumour cell areas and tumour stromal areas was performed in 59 cancer specimens: 32 patients with metastases and 27 patients without metastases. Expression of M-CSF and CSF-1R was recorded as 0 (negative immunoreactivity), 1 (weak), 2 (moderate) or 3 (strong reactivity). Macrophages (CD68) and T lymphocytes (CD3) were detected as proportions of moderately or strongly immunoreactive cells. Patients with metastatic primary cancers showed higher expression of M-CSF (P < 0.0001, P = 0.005), CSF-1R (both P < 0.0001) and CD3 (P = 0.007, P < 0.0001) in both tumour cell areas and tumour stromal areas, compared with the non-metastatic cancers. Conclusions: This study suggests that expression of M-CSF, CSF-1R and CD3 is a significant prognostic factor in primary prostatic cancers by predicting the development of metastases.</p
Editor's Choice – Management of Descending Thoracic Aorta Diseases:Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)
No full textClinical Practice Guidelines of the European Society for Vascular Surgery (ESVS) for the Management of Descending Thoracic Aorta Disease
High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I–III Colon Cancer
No full textColon cancer is a common malignancy and a major contributor to human morbidity and mortality. In this study, we explore the expression and prognostic impact of IRS-1, IRS-2, RUNx3, and SMAD4 in colon cancer. Furthermore, we elucidate their correlations with miRs 126, 17-5p, and 20a-5p, which are identified as potential regulators of these proteins. Tumor tissue from 452 patients operated for stage I–III colon cancer was retrospectively collected and assembled into tissue microarrays. Biomarkers’ expressions were examined by immunohistochemistry and analyzed using digital pathology. In univariate analyses, high expression levels of IRS1 in stromal cytoplasm, RUNX3 in tumor (nucleus and cytoplasm) and stroma (nucleus and cytoplasm), and SMAD4 in tumor (nucleus and cytoplasm) and stromal cytoplasm were related to increased disease-specific survival (DSS). In multivariate analyses, high expression of IRS1 in stromal cytoplasm, RUNX3 in tumor nucleus and stromal cytoplasm, and high expression of SMAD4 in tumor and stromal cytoplasm remained independent predictors of improved DSS. Surprisingly, with the exception of weak correlations (0.2 < r < 0.25) between miR-126 and SMAD4, the investigated markers were mostly uncorrelated with the miRs. However, weak to moderate/strong correlations (0.3 < r < 0.6) were observed between CD3 and CD8 positive lymphocyte density and stromal RUNX3 expression. High expression levels of IRS1, RUNX3, and SMAD4 are positive prognostic factors in stage I–III colon cancer. Furthermore, stromal expression of RUNX3 is associated with increased lymphocyte density, suggesting that RUNX3 is an important mediator during recruitment and activation of immune cells in colon cancer
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