E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP−/− HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification

The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline

QUESTION: What evidence is available regarding the use of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgical resection or chemotherapy for the treatment of recurrent/progressive brain metastases? TARGET POPULATION: This recommendation applies to adults with recurrent/progressive brain metastases who have previously been treated with WBRT, surgical resection and/or radiosurgery. Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy. RECOMMENDATION: Level 3 Since there is insufficient evidence to make definitive treatment recommendations in patients with recurrent/progressive brain metastases, treatment should be individualized based on a patient\u27s functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus non-original site, previous treatment and type of primary cancer, and enrollment in clinical trials is encouraged. In this context, the following can be recommended depending on a patient\u27s specific condition: no further treatment (supportive care), re-irradiation (either WBRT and/or SRS), surgical excision or, to a lesser extent, chemotherapy. Question If WBRT is used in the setting of recurrent/progressive brain metastases, what impact does tumor histopathology have on treatment outcomes? No studies were identified that met the eligibility criteria for this question

Prevalence and morphology of coronary artery ectasia with dual-source CT coronary angiography

To assess the prevalence and morphological characteristics of coronary artery ectasia (CAE) with CT coronary angiography (CTCA) in comparison to conventional catheterangiography (CCA). Dual-source CTCA examinations from 677 consecutive patients (223 women; median age 57 years) were retrospectively evaluated by two blinded observers for the presence of CAE defined as a diameter enlargement >/=1.5 times the diameter of adjacent normal coronary segments. Vessel diameters and contrast attenuation within and proximal to ectatic segments were measured. CCA was used to compare measurements obtained from CTCA with the coronary flow velocity by using the thrombolysis in myocardial infarction (TIMI) frame count. CTCA identified CAE in 20 of 677 (3%) patients. CCA was performed in ten of these patients. CAE diameter measurements with CTCA (10.0 +/- 5.4 mm) correlated significantly (r = 0.92, p < 0.001) with the CCA measurements (8.8 +/- 4.9 mm), but had higher diameters (levels of agreement: -1.0 to 3.4 mm). Contrast attenuation was significantly lower in the ectatic (343 +/- 63 HU) than in the proximal (394 +/- 60 HU) segments (p < 0.01). The attenuation difference significantly correlated with the CAE ratio (r = 0.67, p < 0.01) and the TIMI frame count (r = 0.58, p < 0.05). The prevalence of CAE in a population examined by CTCA is around 3%. Contrast attenuation measurements with CTCA correlate well with the flow alterations assessed with CCA

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer

Background: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin–eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. Methods: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. Results: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. Conclusions: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations

Three-Dimensional Spatial-Spectral Filtering Based Feature Extraction for Hyperspectral Image Classification

Hyperspectral pixels which have high spectral resolution are used to predict decomposition of material types on area of obtained image. Due to its multidimensional form, hyperspectral image classification is a challenging task. Hyperspectral images are also affected by radiometric noise. In order to improve the classification accuracy, many researchers are focusing on the improvement of filtering, feature extraction and classification methods. In the context of hyperspectral image classification, spatial information is as important as spectral information. In this study, a three-dimensional spatial-spectral filtering based feature extraction method is presented. It consists of three main steps. The first is a pre-processing step which include spatial-spectral information filtering in three-dimensional space. The second comprises extract functional features of filtered data. The last one is combining extracted features by serial feature fusion strategy and using to classify hyperspectral image pixels. Experiments were conducted on two popular public hyperspectral remote sensing image, 1%, 5%, 10% and 15% of samples of each classes used as training set, the remaining is used as test set. The proposed method compared with well-known methods. Experimental results show that the proposed method achieved outstanding performance than compared methods in hyperspectral image classification task

Red cell distribution width and neurological scoring systems in acute stroke patients

Hasan Kara,1 Selim Degirmenci,1 Aysegul Bayir,1 Ahmet Ak,1 Murat Akinci,1 Ali Dogru,1 Fikret Akyurek,2 Seyit Ali Kayis3 1Department of Emergency Medicine, Faculty of Medicine, Selcuk University, Konya, Turkey; 2Department of Biochemistry, Faculty of Medicine, Selcuk University, Konya, Turkey; 3Department of Biostatistics, Faculty of Medicine, Karabuk University, Karabuk, Turkey Objectives: The purpose of the present study was to evaluate the association between the red blood cell distribution width (RDW) and the Glasgow Coma Scale (GCS), Canadian Neurological Scale (CNS), and National Institutes of Health Stroke Scale (NIHSS) scores in patients who had acute ischemic stroke. Methods: This prospective observational cohort study included 88 patients who have had acute ischemic stroke and a control group of 40 patients who were evaluated in the Emergency Department for disorders other than acute ischemic stroke. All subjects had RDW determined, and stroke patients had scoring with the GCS, CNS, and NIHSS scores. The GCS, CNS, and NIHSS scores of the patients were rated as mild, moderate, or severe and compared with RDW. Results: Stroke patients had significantly higher median RDW than control subjects. The median RDW values were significantly elevated in patients who had more severe rather than milder strokes rated with all three scoring systems (GCS, CNS, and NIHSS). The median RDW values were significantly elevated for patients who had moderate rather than mild strokes rated by GCS and CNS and for patients who had severe rather than mild strokes rated by NIHSS. The area under the receiver operating characteristic curve was 0.760 (95% confidence interval, 0.676&ndash;0.844). Separation of stroke patients and control groups was optimal with RDW 14% (sensitivity, 71.6%; specificity, 67.5%; accuracy, 70.3%). Conclusion: In stroke patients who have symptoms &lt;24 hours, the RDW may be useful in predicting the severity and functional outcomes of the stroke. Keywords: cerebrovascular accident, hematology, prognosis, severity&nbsp

High-sensitivity C-reactive protein, lipoprotein-related phospholipase A2, and acute ischemic stroke

Hasan Kara,1 Murat Akinci,1 Selim Degirmenci,1 Aysegul Bayir,1 Ahmet Ak,1 Alaaddin Nayman,2 Ali Unlu,3 Fikret Akyurek,3 Mesut Sivri2 1Department of Emergency Medicine, 2Department of Radiology, 3Department of Biochemistry, Faculty of Medicine, Sel&ccedil;uk University, Konya, Turkey Background: Serum biomarkers may be useful for early diagnosis of acute ischemic stroke, exclusion of other diseases that may mimic stroke, and prediction of infarct volume. We evaluated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-related phospholipase A2&nbsp;(Lp-PLA2)&nbsp;in patients who had acute ischemic stroke.Methods: In 200 patients who presented to an emergency service (acute ischemic stroke, 102&nbsp;patients; control with no stroke, 98 patients), stroke patients were evaluated with the Canadian neurological scale and diffusion-weighted magnetic resonance imaging, and all patients were evaluated with the Glasgow coma scale and their serum hs-CRP level and Lp-PLA2&nbsp;activity were assessed. The volume of stroke lesions was calculated from magnetic resonance images.Results: Patients who had stroke had higher mean serum hs-CRP level (stroke, 7&plusmn;6&nbsp;mg/dL; &shy;control, mean &plusmn; standard deviation 1&plusmn;1&nbsp;mg/dL; P&le;0.001) and Lp-PLA2&nbsp;activity (stroke, mean &plusmn; standard deviation 113&plusmn;86&nbsp;nmol/min/mL; control, mean &plusmn; standard deviation 103&plusmn;50&nbsp;nmol/min/mL; P&le;0.001) than control patients who did not have stroke. The mean hs-CRP level and Lp-PLA2&nbsp;activity were higher in patients who had greater stroke severity (lower Canadian neurological scale score) and were higher in patients who had larger volume strokes. Conclusion: Higher hs-CRP level and Lp-PLA2&nbsp;activity are significantly associated with more severe neurologic impairment and larger infarct size in patients who have acute ischemic stroke. These biomarkers may be useful for rapid diagnosis and prediction of ischemic tissue volume in the early stage of ischemic stroke. These findings may be important for health care facilities that have limited access to emergency computed tomography scanning for the diagnosis of stroke. Keywords: cerebrovascular accident, atherosclerosis, inflammation, biomarke

Radiation Therapy and Chemotherapy Results in Elderly Patients With Stage III Non-Small Cell Lung Cancer: Turkish Thoracic Radiation Oncology Group Study

58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) -- SEP 25-28, 2016 -- Boston, MAWOS: 000387655803461Amer Soc Radiat Onco