Serum sICAM, sVCAM and sE-selectin levels in colorectal cancer patients.

Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and the fourth cause of cancers death in the world. Soluble adhesion molecules (CAMs) are thought to have an important role in host defense against carcinogenesis. They are biomarkers of inflammation and indicators of the immune response to tumors. The study included 40 CRC patients without remote metastases and 24 control subjects. Serum concentrations of sE-selectin, sICAM and sVCAM in patients with CRC were investigated by ELISA method. The level of the sCAMs decreased significantly after radical tumor resection. Preoperative serum concentrations of sICAM and sVCAM in CRC patients were significantly higher compared to the control group, whereas there were no differences regarding serum sE-selectin. Serum levels of sE-selectin, sICAM and sVCAM correlated significantly with each other. There was a significant correlation of serum levels of sICAM-1 and sVCAM-1, but not sE-selectin, with TNM stage and lymph node involvement. No significant relationship was found between serum concentrations of sICAM-1, sVCAM-1 and sE-selectin in CRC patients and patients' age or gender. Our findings suggest that an improved understanding of the mechanisms of membrane shedding of sICAM, sVCAM and sE-selectin is required to delineate their role in tumor progression

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture

Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell populations that had been selected for TRAIL-resistance from initially TRAIL-sensitive populations. SAHA may increase TRAIL sensitivity in insensitive cells, but not in cells that have specifically been selected for acquired TRAIL-resistance. [Abstract copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor

[EN] Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p < 0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios.This work received financial support from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (DPI2015-68397-R), VLC/Campus (UPV-FE-2018-B03) and by Conselleria de Educación, Investigación, Cultura y Deporte, Generalitat Valenciana (GV/2018/104).Mas-Cabo, J.; Prats-Boluda, G.; Ye Lin, Y.; Alberola Rubio, J.; Perales, A.; Garcia-Casado, J. (2019). Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor. Biomedical Signal Processing and Control. 52:198-205. https://doi.org/10.1016/j.bspc.2019.04.001S1982055

Uterine electromyography for discrimination of labor imminence in women with threatened preterm labor under tocolytic treatment

[EN] As one of the main aims of obstetrics is to be able to detect imminent delivery in patients with threatened preterm labor, the techniques currently used in clinical practice have serious limitations in this respect. The electrohysterogram (EHG) has now emerged as an alternative technique, providing relevant information about labor onset when recorded in controlled checkups without administration of tocolytic drugs. The studies published to date mainly focus on EHG-burst analysis and, to a lesser extent, on whole EHG window analysis. The study described here assessed the ability of EHG signals to discriminate imminent labor (The ability of EHG recordings to predict imminent labor (<7days) was analyzed in preterm threatened patients undergoing tocolytic therapies by means of EHG-burst and whole EHG window analysis. The non-linear features were found to have better performance than the temporal and spectral parameters in separating women who delivered in less than 7days from those who did not.Mas-Cabo, J.; Prats-Boluda, G.; Perales Marín, AJ.; Garcia-Casado, J.; Alberola Rubio, J.; Ye Lin, Y. (2019). Uterine electromyography for discrimination of labor imminence in women with threatened preterm labor under tocolytic treatment. Medical & Biological Engineering & Computing. 57:401-411. https://doi.org/10.1007/s11517-018-1888-yS40141157Aboy M, Cuesta-Frau D, Austin D, Micó-Tormos P (2007) Characterization of sample entropy in the context of biomedical signal analysis. Conf Proc IEEE Eng Med Biol Soc:5942–5945. https://doi.org/10.1109/IEMBS.2007.4353701Aboy M, Hornero R, Abásolo D, Álvarez D (2006) Interpretation of the Lempel-Ziv complexity measure in the context of biomedical signal analysis. 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BJOG 112:10–15. https://doi.org/10.1111/j.1471-0528.2005.00577.xRabotti C, Sammali F, Kuijsters N, et al (2015) Analysis of uterine activity in nonpregnant women by electrohysterography: a feasibility study. In: Proc Annu Int Conf IEEE Eng Med Biol Soc EMBS pp 5916–5919Schlembach D, Maner WL, Garfield RE, Maul H (2009) Monitoring the progress of pregnancy and labor using electromyography. Eur J Obstet Gynecol Reprod Biol 144:2–8. https://doi.org/10.1016/j.ejogrb.2009.02.016Sikora J, Matonia A, Czabański R et al (2011) Recognition of premature threatening labour symptoms from bioelectrical uterine activity signals. Arch Perinat Med 17:97–103Vinken MPGC, Rabotti C, Mischi M, van Laar JOEH, Oei SG (2010) Nifedipine-induced changes in the electrohysterogram of preterm contractions: feasibility in clinical practice. Obstet Gynecol Int 2010:325635. https://doi.org/10.1155/2010/325635Vrhovec J, Lebar AM (2012) An uterine electromyographic activity as a measure of labor progression. 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Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregnant women

BACKGROUND: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound. OBJECTIVE: To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term. METHODS: Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin, administration to isolated myometrial strips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA(2) values were calculated. RESULTS: Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA(2) value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA(2), results were 9.89 and 7.8 1, respectively. None of these pA(2) values differed to any statistically significant degree. CONCLUSION: The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor. Copyright (C) 2004 by the Society for Gynecologic Investigation

Decreased serum level of macrophage inflammatory chemokine-3 beta/CCL19 in preterm labor and delivery

Objective: Chemokines are small soluble molecules which mediate leukocyte migration and may be involved in the pathophysiology of preterm labor. We aimed to determine if serum concentrations of selected chemokines are changed in preterm labor and delivery. Study design: A novel array-based enzyme-linked immunosorbent assay was used to quantitate serum levels of nine chemokines from a single sample: MDC/CCL22, TARC/CCL17, ITAC/CXCL11, 1-309/CCL1, IP-10/CXCL10, MIP-1 alpha/CCL3, -1 beta/CCL4, -3 alpha/CCL20 and -3 beta/CCL19. Women in preterm labor who delivered (n = 17), women at preterm pregnancy not in labor (n = 13) and women in labor at term (n = 8) participated. Results: In the preterm delivery group of patients, the MIP-3 beta/CCL19 concentration was in mean (+/- S.D.) 70.4 +/- 31.7 pg/mL, which was significantly lower than that in preterm gravidas not in labor of 123 +/- 34 pg/mL (p < 0.001) and those in labor at term of 118 +/- 25.6 pg/mL (p < 0.01). The other measured chemokines did not differ significantly. Conclusions: Of a small number of examined chemokines, we were able to show that one of them, MIP-3 beta/CCL19 was significantly lower in women with preterm labor and delivery. Whether or not this chemokine has a potential as biochemical marker of preterm delivery remains to be determined. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery.

Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I - pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II - threatened preterm labour patients between 24-34 weeks of gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery