Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance ...of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy.
The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability.
Multivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR.
Cellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.
The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort.
The study ...comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan-Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis.
The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan-Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis.
The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth of a variety of cells in an autocrine or paracrine manner. Although HB-EGF is widely ...expressed in tumors compared with normal tissue, its contribution to tumorigenicity is unknown. HB-EGF can be produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (s-HB-EGF), although a significant amount of pro-HB-EGF remains uncleaved on the cell surface. To understand the roles of two forms of HB-EGF in promoting tumor growth, we have studied the effects of HB-EGF expression in the process of tumorigenesis using in vitro and in vivo systems. We demonstrate here that in EJ human bladder cancer cells containing a tetracycline-regulatable s-HB-EGF or pro-HB-EGF expression system, s-HB-EGF expression increased their transformed phenotypes, including growth rate, colony-forming ability, and activation of cyclin D1 promoter, as well as induction of vascular endothelial growth factor in vitro. Moreover, s-HB-EGF or wild-type HB-EGF induced the expression and activities of the metalloproteases, MMP-9 and MMP-3, leading to enhanced cell migration. In vivo studies also demonstrated that tumor cells expressing s-HB-EGF or wild-type HB-EGF significantly enhanced tumorigenic potential in athymic nude mice and exerted an angiogenic effect, increasing the density and size of tumor blood vessels. However, cells expressing solely pro-HB-EGF did not exhibit any significant tumorigenic potential. These findings establish s-HB-EGF as a potent inducer of tumor growth and angiogenesis and suggest that therapeutic intervention aimed at the inhibition of s-HB-EGF functions may be useful in cancer treatment.
High-quality Zn1−xCoxO (ZnCoO) thin films with different Co concentrations (x=0−0.07) were synthesized on Al2O3 substrates using a radio-frequency magnetron sputtering process. The structural, ...chemical, optical, and electrical properties of the films were characterized using various techniques. High-resolution X-ray diffraction measurements showed that the ZnCoO films had a c-oriented hexagonal wurtzite structure with no extra phases. The lattice constants of the films increased slightly with increasing the Co concentration ratio. X-ray photoelectron spectra show the incorporation of Co2+ ions in the ZnO host without the formations of Co clusters. Hall measurements revealed that the films were n-type with a charge carrier density of ∼2.6×1018 per cm3. A neutral-donor bound exciton peak (D0X) from all specimens was observed at 3.36eV using photoluminescence measurements at 10K. The physical and chemical properties of the films suggested that their ferromagnetic properties originated from a direct exchange interaction between magnetic Co ions.
► High-quality ZnCoO film growth using RF sputtering process. ► ZnCoO films are sing crystals with no extra phases. ► XPS confirms the chemical valence state of Co2+. ► Hall measurements revealed n-type semiconductors. ► The ferromagnetic properties of the films are induced by the direct interaction between Co ions.
This study examined the structural properties of ZnO nanorods grown on Ti-buffer layers with different surface roughnesses of 1.5 and 4.0
nm. Vertically aligned ZnO nanorods were synthesized on Al
2O
...3 substrates with a Ti-buffer layer by metal-organic chemical vapor deposition. X-ray diffraction revealed the ZnO nanorods grown on a smooth surface to have higher quality and better alignment in the
ab-plane than those grown on the rough surface. Field-emission transmission electron microscopy (FE-TEM) measurements revealed a disordered layer at the ZnO/Ti interface. FE-TEM demonstrated that the Ti-buffer layer contained a mixture of ordered and amorphous phases. Energy dispersive spectroscopy (EDS) analysis revealed the Ti-buffer layers to be entirely oxides.
We identified IFI16 as a BRCA1-associated protein involved in p53-mediated apoptosis. IFI16 contains the Pyrin/PAAD/DAPIN domain, commonly found in cell death-associated proteins. BRCA1 (aa 502-802) ...interacted with the IFI16 Pyrin domain (aa 1-130). We found that IFI16 was localized in the nucleoplasm and nucleoli. Clear nucleolar IFI16 localization was not observed in HCC1937 BRCA1 mutant cells, but reintroduction of wild-type BRCA1 restored IFI16 nuclear relocalization following IR (ionizing radiation). Coexpression of IFI16 and BRCA1 enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1 mutant mice expressing wild-type p53, although mutant IFI16 deficient in binding to BRCA1 did not induce apoptosis. Furthermore, tetracycline-induced IFI16 collaborated in inducing apoptosis when adenovirus p53 was expressed in DNA-damaged p53-deficient EJ cells. These results indicate a BRCA1-IFI16 role in p53-mediated transmission of DNA damage signals and apoptosis.
Creating a prosthetic device for the blind is a central future task. Our research examines the feasibility of producing a prosthetic device based on electrical stimulation of primary visual cortex ...(area V1), an area that remains intact for many years after loss of vision attributable to damage to the eyes. As an initial step in this effort, we believe that the research should be carried out in animals, as it has been in the creation of the highly successful cochlear implant. We chose the rhesus monkey, whose visual system is similar to that of man. We trained monkeys on two tasks to assess the size, contrast, and color of the percepts created when single sites in area V1 are stimulated through microelectrodes. Here, we report that electrical stimulation within the central 5° of the visual field representation creates a small spot that is between 9 and 26 min of arc in diameter and has a contrast ranging between 2.6% and 10%. The dot generated by the stimulation in the majority of cases was darker than the background viewed by the animal and was composed of a variety of low-contrast colors. These findings can be used as inputs to models of electrical stimulation in area V1. On the basis of these findings, we derive what kinds of images would be expected when implanted arrays of electrodes are stimulated through a camera attached to the head whose images are converted into electrical stimulation using appropriate algorithms.
Desiccation of plants during drought can be detrimental to agricultural production. The phytohormone abscisic acid (ABA) reduces water loss by triggering stomatal pore closure in leaves, a process ...requiring ion-channel modulation by cytoplasmic proteins. Deletion of the Arabidopsis farnesyltransferase gene ERA1 or application of farnesyltransferase inhibitors resulted in ABA hypersensitivity of guard cell anion-channel activation and of stomatal closing. ERA1 was expressed in guard cells. Double-mutant analyses of era1 with the ABA-insensitive mutants abi1 and abi2 showed that era1 suppresses the ABA-insensitive phenotypes. Moreover, era1 plants exhibited a reduction in transpirational water loss during drought treatment
PD is associated with a variety of sleep problems. The dopamine agonists (DA) pramipexole and ropinirole were recently implicated in causing "sleep attacks" and motor vehicle accidents.
In order to ...determine the overall rate of subjective sleep problems in PD and to determine if any factors, including specific medications, correlate with sleep pathology, the authors surveyed consecutive patients with PD seen over a 3-month period in a Movement Disorders Clinic. The authors collected demographic and medication data, and the patients completed the Epworth Sleepiness Scale (ESS), questions assessing the presence of restless legs syndrome (RLS), a modified National Sleep Foundation sleep survey, and specific questions regarding falling asleep while driving.
A total of 320 patients completed the questionnaire. The authors eliminated 17, six for incomplete data and 11 for having a primary diagnosis other than PD. The mean age of the remaining 303 patients was 67.1 +/- 10.7 years, and the mean duration of PD was 9.1 +/- 5.7 years. The ESS scores averaged 11.1 +/- 5.9, and in 50.2% of patients the score was abnormally high (>10). Stepwise regression analysis found that sleepiness correlated with longer duration of PD (p < 0.001), more advanced PD (p < 0.004), male sex (p < 0.001), and the use of any DA (p < 0.003). The soporific effects of the three most common DA (pramipexole, ropinirole, and pergolide) were similar. Falling asleep while driving was reported by 63/279 (22.6%) of current drivers and correlated with higher ESS scores (p < 0.05). Other sleep disorders, including RLS, were also frequently reported.
Daytime sleepiness is common in PD and correlates with more advanced and longer duration of PD, and male sex. The DA were also independently associated with daytime sleepiness, but in this group, no single DA was more culpable than the others.
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