In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy ...significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal. These breast tissue specimens have been profiled for their microRNA (miR) expression, in search of differentially expressed miR among patients treated or not with IORT. Our results demonstrate that IORT elicits effects that go beyond the direct killing of residual tumor cells. IORT altered the wound response, inducing the expression of miR-223 in the peri-tumoral breast tissue. miR-223 downregulated the local expression of epidermal growth factor (EGF), leading to decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EGF-EGFR autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. Accordingly, both RT-induced miR-223 and peri-operative inhibition of EGFR efficiently prevented BC cell growth and reduced recurrence formation in mouse models of BC. Our study uncovers unknown effects of RT delivered on a wounded tissue and prompts to the use of anti-EGFR treatments, in a peri-operative treatment schedule, aimed to timely treat BC patients and restrain recurrence formation.
•MB in different concentration, activated or not, did not influence the bond strength.•MB100L group showed difference among the root canal thirds for bond strength.•Mixed failure was prevalent for MB ...regardless the PS concentration activated or not.•MB100L showed lower qualitative penetration of MTA sealer into root dentin tubules.
Photodynamic therapy (PDT) is used as an adjunct to endodontic treatment to enhance microbial reduction in the root canal system. However, studies evaluating the impact of PDT on the bond strength of the canal sealer to intraradicular dentin are scarce. Thus, this in vitro study aimed to evaluate the influence of photodynamic therapy with methylene blue (MB) photosensitizer (PS) on the bond strength and morphology of the interface between mineral trioxide aggregate (MTA) based endodontic sealer and different thirds of intraradicular dentin.
Fifty-five bovine incisors were used to simulate experimental endodontic treatments. Biomechanical instrumentation was performed in all root canals and teeth were divided into 5 groups (n = 11): deionized water (control), methylene blue 50 mg/L (MB50WL), methylene blue 100 mg/L (MB100WL), methylene blue 50 mg/L + red laser (MB50L), and methylene blue 100 mg/L + red laser (MB100L). The push-out bond strength of canal sealer to intraradicular dentin was measured using a universal testing machine (n = 8). Representative scanning electron microscopy images were obtained to qualify the fracture patterns. Images of the adhesive interface morphology were obtained using confocal laser scanning microscopy (n = 3). The Kruskal-Wallis test was used to compare data on bond strength between groups, and the Friedman test between thirds (α = 0.05).
When comparing root thirds for the MB group with the higher concentration activated by red laser, higher bond strength values was found for the apical third than for the middle third (P = 0.0302). MB in different concentrations, activated by red laser or not, had no influence on the bond strength of distinct thirds of the intraradicular dentin (P > 0.05). As for the adhesive interface morphology, the MB100L group showed a lower qualitatively sealer penetration into the intraradicular dentin.
PDT with MB PS at 50 mg/L had no negative impact on the bond strength of MTA Fillapex canal sealer to intraradicular dentin, being a suitable antisepsis protocol for endodontic treatments.
The mitotic cell cycle is a tightly regulated process that ensures the correct division of one cell into two daughter cells. Progress along the different phases of the cell cycle is positively ...regulated by the sequential activation of a family of serine-threonine kinases called CDKs (Cyclin Dependent Kinases). Their activity is counteracted by small proteins known as CDK inhibitors (CKI) that ensure the correct timing of CDK activation in the different phases of the cell cycle. The present review will deal with the role of one of this CKI, p27(kip1), in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells. p27(kip1) protein downregulation is usually achieved by proteasomal degradation and is often correlated to a worse prognosis in several types of human cancers, resulting in the reduction of disease free and overall survival. More recently, it has been proposed that p27(kip1) protein, rather than degraded, can be functionally inactivated. The mechanisms and the implications of these two types of p27(kip1) deregulation will be discussed and some potential therapeutic approaches targeting p27(kip1) functions will be proposed.
Abstract We have tested the hypothesis that human early trophoblast is a target for somatostatin (SRIF) regulatory actions. We report for the first time that SSTR2A and 2B transcripts and proteins ...are present in first-trimester human chorionic villi and the trophoblast-derived HTR-8/SVneo and JAR cells. In both cell lines, SSTR are functional since SRIF inhibits cyclic AMP pathway, stimulates arachidonic acid release and enhances cell proliferation. Moreover, in HTR-8/SVneo cells, considered a good model of first-trimester EVT, SRIF also enhances migration. An involvement of the cyclic AMP pathway in mediating SRIF effects on proliferation and migration is suggested. Our data support the idea that SRIF regulates early trophoblast functions mainly through an interaction with SSTR2.
The mitotic cell cycle is a tightly regulated process that ensures the correct division of one cell into two daughter cells. Progress along the different phases of the cell cycle is positively ...regulated by the sequential activation of a family of serine-threonine kinases called CDKs (Cyclin Dependent Kinases). Their activity is counteracted by small proteins known as CDK inhibitors (CKI) that ensure the correct timing of CDK activation in the different phases of the cell cycle. The present review will deal with the role of one of this CKI, p27kip1, in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells. p27kip1 protein downregulation is usually achieved by proteasomal degradation and is often correlated to a worse prognosis in several types of human cancers, resulting in the reduction of disease free and overall survival. More recently, it has been proposed that p27kip1 protein, rather than degraded, can be functionally inactivated. The mechanisms and the implications of these two types of p27kip1 deregulation will be discussed and some potential therapeutic approaches targeting p27kip1 functions will be proposed.
A random lattice is used to model moisture transport in cement-based composites. Model geometry, and the scaling of the elemental diffusivity terms, are based on a Voronoi discretization of the ...material domain. Steady-state and transient potential flow problems are simulated, and compared with theory, to demonstrate model accuracy and objectivity with respect to lattice random geometry. A novel routine is described for computing moisture flux values at the random lattice sites.
Stress production, and potential shrinkage crack development, are driven by the associated drying processes. The random lattice modeling of moisture movement is coupled with rigid-body-spring networks (RBSN), which account for elasticity, creep, and fracture properties of the material. The RBSN is based on the same Voronoi discretization of the material as used to model moisture movement. Relative humidity contours, stress contours, and crack plots are produced for a cement composite overlay restrained by a mature concrete substrate. That example is based on a set of simulation results reported in the literature.
Elevated heart rate (HR) has been found to be related to an increased death rate in patients with acute myocardial infarction (AMI), but sex differences and optimal timing for HR measurement have not ...been sufficiently investigated.
To verify the predictive value of HR for one-year mortality in a cohort of subjects hospitalized for AMI, with men and women considered separately.
HR was measured in 424 patients (303 men and 121 women) with constant sinus HR, on the first, third and seventh days after hospital admission for AMI. Clinical and laboratory data were obtained on the same days. All patients were followed up for one year.
Among the men, the one-year mortality rate was 5% for the subjects with a seven-day HR of less than 80 beats/min, and the one-year mortality rate was 39% for patients with a seven- day HR of 80 beats/min or more (P<0.0001). Among the women, the differences in mortality related to HR were not significant. In a multivariate Cox regression analysis, the relative risks of mortality in men who had an HR of 80 beats/min or more were 3.1 (CI=1.4 to 7.0, P=0.003) on the first day, 4.1 (CI=1.8 to 9.8, P=0.001) on the third day and 8.6 (CI=2.9 to 27.0, P<0.0001) on the seventh day. In the 203 men in whom echocardiographic left ventricular ejection fraction was measured, an interactive effect of high HR with depressed ejection fraction on mortality was found. Beta-blocking therapy influenced HR during AMI but did not influence the HR-mortality association.
The results of the present prospective study show that HR measured during the first week after admission for AMI is an important predictor of mortality in men. The predictive power of HR increased from the first to the seventh day after AMI.
Seismic protection systems include the use of special passive devices to introduce supplemental damping into the structure. In building applications, passive devices are normally used in brace ...configurations and activated by a component of the structural drift. However, in applications where small elastic interstory displacements are expected, the conventional usage of such devices may not be suitable. Lever mechanisms, which amplify the displacements and velocities affecting the damping device, can be employed to overcome this deficiency. This work describes a displacement amplification device (DAD) based on a gear-type mechanism and connected in series with a fluid viscous damper (FVD). Laboratory test results are given here for a small-scale version of the DAD-FVD system. Potential implementations of this amplification system in civil structures are briefly described.
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