Nuclear Localization of CXCR4 Determines Prognosis for Colorectal Cancer Patients

Chemokines and their receptors are implicated in formation of colorectal cancer metastases. Especially CXCR4 is an important factor, determining migration, invasiveness, metastasis and proliferation of colorectal cancer cells. Object of this study was to determine expression of CXCR4 in tumor tissue of colorectal cancer patients and associate CXCR4 expression levels to clinicopathological parameters. Levels of CXCR4 expression of a random cohort of patients, who underwent primary curative resection of a colorectal carcinoma, were retrospectively determined by quantitative real-time RT-PCR and semi-quantitative analyses of immunohistochemical stained paraffin sections. Expression levels were associated to clinicopathological parameters. Using RT-PCR we found that a high expression of CXCR4 in the primary tumor was an independent prognostic factor for a poor disease free survival (p = 0.03, HR: 2.0, CI = 1.1–3.7). Immunohistochemical staining showed that nuclear distribution of CXCR4 in the tumor cells was inversely associated with disease free and overall survival (p = 0.04, HR: 2.6, CI = 1.0–6.2), while expression in the cytoplasm was not associated with prognosis. In conclusion, our study showed that a high expression of nuclear localized CXCR4 in tumor cells is an independent predictor for poor survival for colorectal cancer patients

Angiopoietin-1 promotes functional neovascularization that relieves ischemia by improving regional reperfusion in a swine chronic myocardial ischemia model

10.1007/s11373-006-9082-xJournal of Biomedical Science134579-59

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Effect of Mn on <100> Texture Evolution in Fe-Si-Mn Alloys

The texture can be evolved through the gamma to a transformation by cooling in Fe-Si alloy systems. Oxygen in the annealing atmosphere hampers the evolution of the texture. The texture evolution is associated with the fact that the {100} faces are elastically compliant so that the texture can develop in a manner consistent with minimization of strain energy. By alloying Mn to Fe-Si alloys, the texture evolves in relatively high oxygen containing annealing atmosphere. The role of Mn in the texture evolution appears to be preventing formation of surface oxides, which modify the elastic modulus of metal surface, thereby suppress the development of the correct texture.1111sciescopu

A central back-coupling hypothesis on the organization of motor synergies: a physical metaphor and a neural model

We offer a hypothesis on the organization of multi-effector motor synergies and illustrate it with the task of force production with a set of fingers. A physical metaphor, a leaking bucket, is analyzed to demonstrate that an inanimate structure can show apparent error compensation among its elements. A neural model is developed using tunable back-coupling loops as means of assuring error compensation in a task-specific way. The model demonstrates non-trivial features of multi-finger interaction such as delayed emergence of force stabilizing synergies and simultaneous stabilization of the total force and total moment produced by the fingers. The hypothesis suggests that neurophysiological structures involving short-latency feedback may play a central role in the formation of motor synergies

Efficacy and Safety of Prostatic Arterial Embolization: Systematic Review with Meta-Analysis and Meta-Regression

Purpose: This study attempted to overcome the limitations of previous systematic reviews to determine the overall treatment efficacy and safety of prostatic arterial embolization compared with standard therapy. Materials and Methods: Meta-analyses were done of randomized, controlled and single group trials. Meta-regression analysis of the moderator effect was performed with single group analysis. The outcomes measured were mean changes in I-PSS (International Prostate Symptom Score), quality of life, maximal urinary flow rate, prostate volume, post-void residual volume and prostate specific antigen. Adverse events were compared as proportional differences between the embolization group and groups receiving other therapies in comparative studies. Results: A total of 16 studies met our selection criteria and were included in the meta-analysis. Three studies were comparative and included a total of 297 subjects, including 149 in the experimental groups and 148 in the control groups. The other 13 studies were noncomparative and included a total of 750 experimental subjects. Pooled overall standardized mean differences for embolization in I-PSS, maximal urinary flow rate and prostate volume were significantly impaired in the experimental vs control groups. Overall weighted mean differences for all outcomes except prostate specific antigen were significantly improved from baseline by embolization treatment in noncomparative studies. Sensitivity analysis of study duration showed that all outcome measurements did not differ before vs after 6 months. Conclusions: Although there is growing evidence of the efficacy and safety of prostatic arterial embolization for benign prostatic hyperplasia, this systematic review using meta-analysis and meta-regression showed that prostatic arterial embolization should still be considered an experimental treatment modality.11148sciescopu

Effect Of Carbon Nanotubes On The Properties Of Spark Plasma Sintered ZrO2/CNT Composites

Zirconia matrix ZrO2/CNT composite materials reinforced with multiwall carbon nanotubes were fabricated using a spark plasma sintering technique. The effects of the amount of CNTs addition, sintering temperature and sintering pressure on the properties of the resulting ZrO2/CNT composites were examined. 0 to 9 vol. % CNTs were dispersed in zirconia powder, and the resulting mixture was sintered. The electrical conductivity, hardness, flexural strength, and density were measured to characterize the composites. The friction and wear properties of the composites were also tested. The flexural strength and friction coefficient of the composites were improved with up to 6 vol.% of CNT addition and the flexural strength showed a close relationship with the relative density of the composite. The electrical conductivity increased with increasing proportion of the CNTs, but the efficiency was reduced at more than 6 vol.% CNTs