18272 research outputs found
Sort by
ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma
Full text linkPURPOSE: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.
EXPERIMENTAL DESIGN: To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.
RESULTS: Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).
CONCLUSIONS: Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice
Family history of cancer and the risk of childhood brain tumors: a pooled analysis of the ESCALE and ESTELLE studies (SFCE)
Full text linkPURPOSE: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated.
METHODS: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.
RESULTS: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings.
CONCLUSION: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier
Seed quality and carbon primary metabolism
Full text linkImproving seed quality is amongst the most important challenges of contemporary agriculture. In fact, using plant varieties with better germination rates that are more tolerant to stress during seedling establishment may improve crop yield considerably. Therefore, intense efforts are currently being devoted to improve seed quality in many species, mostly using genomics tools. However, despite its considerable importance during seed imbibition and germination processes, primary carbon metabolism in seeds is less studied. Our knowledge of the physiology of seed respiration and energy generation and the impact of these processes on seed performance have made limited progress over the past three decades. In particular, (isotope‐assisted) metabolomics of seeds has only been assessed occasionally, and there is limited information on possible quantitative relationships between metabolic fluxes and seed quality. Here, we review the recent literature and provide an overview of potential links between metabolic efficiency, metabolic biomarkers, and seed quality and discuss implications for future research, including a climate change context
Human macrophages and osteoclasts resorb β-tricalcium phosphate in vitro but not mouse macrophages
Full text linkβ-TCP is a resorbable bony biomaterial but its biodegradation mechanisms in vivo remains unclear. Osteoclast can resorb β-TCP but a role for macrophages has also been suggested by in vivo studies. However no in vitro study has clearly evidenced the action of macrophages in the resorption process. We prepared flat β-TCP tablets with a smooth surface to investigate the in vitro capability of murine (RAW 264.7) and human macrophage cells (PBMCs) to resorb the biomaterial. In parallel, these cells were differentiated into multinucleated osteoclasts with M-CSF and RANK-L. The action of these cells was evaluated by scanning electron microscopy and Raman microspectroscopy after a 21 day culture on the tablets. Human macrophages and osteoclasts derived from PBMCs appeared able to resorb β-TCP by forming resorption pits at the surface of the flat tablets. RAW macrophages were unable to resorb β-TCP but they exhibited this possibility when they have been differentiated into osteoclasts. These cells can engulf β-TCP grains in their cytoplasm as evidenced by light and TEM microscopy with production of carbonic anhydrase (revealed by the immunogold technique in TEM). The resorbed areas were characterized by severe degradation of the grains showing speckled and stick-like aspects indicating a chemical corrosion. The effect was maximal at the grain boundaries which have a slightly different chemical composition. Changes in the Raman spectrum were observed between the resorbed and un-resorbed β-TCP suggesting crystal modifications. In contrast, un-differentiated murine macrophages were not able to chemically attack β-TCP and no resorption pit was observed. RAW cell is not a representative model of the macrophage-biomaterial interactions that occur in human. This in vitro study evidences that both human osteoclasts and macrophages represent active cell populations capable to resorb β-TCP
Positron Emission Tomography/Computed Tomography with Gallium-68-labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model
Full text linkBACKGROUND: Evaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques.
OBJECTIVE: We assessed whether positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen (Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP).
DESIGN, SETTING, AND PARTICIPANTS: A total of 1×10 LNCaP cells were grafted subcutaneously in the flanks of 6-8-wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance.
RESULTS AND LIMITATIONS: Four weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01).
CONCLUSIONS: In a preclinical prostate cancer model, we show that Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials.
PATIENT SUMMARY: Positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer
Modèles anciens et nouvelle leçon de vie : la uirtus, des premiers apologistes latins à Lactance, le « Cicéron chrétien
Full text linkDriving and use of the mobile phone: a study among 18 to 24-year-old
Full text linkWhile we know that using the telephone when driving increases the risk of accidents and that 18 to 24 year-olds are a fringe of the population that is particularly affected by fatal accidents on the road, we lack information concerning the use of the mobile phone in this age group. This study carried out with 208 young drivers aims to gather data, analyses their behavior at the wheel with the mobile plus their beliefs and awareness of risk. Three contexts are focused on: stopping at the red light, driving during the rush hour and highways. The findings highlight the importance of messaging and the influence of the context on the use of the mobile. We observe an inverse effect between the speed and messaging. While young people declare they are aware of certain risks, it concerns more the risks penalties and accordingly they appear to be impervious to road safety campaigns concerning the mobile phone behind the wheel. On this subject few major differences are to be found between male and female drivers and between very young and young drivers. The use of the mobile while driving among 18 to 24-year-olds therefore presents universal characteristics of use from moment or the driver (male or female) is a little more experimented
State of knowledge on smartphone applications concerning contraception: A systematic review
Full text linkAIM: Women\u27s knowledge of contraception is incomplete and a wide variety of information sources are used. Since the advent of smartphones, 325,000 healthcare apps have become available. Our aim is to conduct a literature review on smartphone applications for contraception.
METHODS: 15 databases in English, Spanish and French were examined, which included studies published between 2007 and 2018 that describe or compare mobile applications for reversible contraceptive methods and interventional studies. The quality of the studies was assessed using the Cochrane scale or a scale created by the authors.
RESULTS: 1786 articles were listed and 22 were included in the main text. In two randomised controlled trials, apps did not influence the choice of a contraceptive method. Two studies showed a significant improvement in knowledge after using an app. Comparative studies reported a large number of apps, the majority of which contained only incomplete information and few interactive features.
CONCLUSION: Many applications deal with contraception, but few have reliable and exhaustive information. Further studies are needed to measure the impact of apps on observing compliance
