Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

<p>Abstract</p> <p>Background</p> <p>To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.</p> <p>Methods</p> <p>A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).</p> <p>Results</p> <p>Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.</p> <p>Conclusions</p> <p>PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.</p

Spin flop and crystalline anisotropic magnetoresistance in CuMnAs

Recent research works have shown that the magnetic order in some antiferromagnetic materials can be manipulated and detected electrically, due to two physical mechanisms: Neel-order spin-orbit torques and anisotropic magnetoresistance. While these observations open up opportunities to use antiferromagnets for magnetic memory devices, different physical characterization methods are required for a better understanding of those mechanisms. Here we report a magnetic field induced rotation of the antiferromagnetic Neel vector in epitaxial tetragonal CuMnAs thin films. Using soft x-ray magnetic linear dichroism spectroscopy, x-ray photoemission electron microscopy, integral magnetometry and magneto-transport methods, we demonstrate spin-flop switching and continuous spin reorientation in antiferromagnetic films with uniaxial and biaxial magnetic anisotropies, respectively. From field-dependent measurements of the magnetization and magnetoresistance, we obtain key material parameters including the anisotropic magnetoresistance coefficients, magnetocrystalline anisotropy, spin-flop and exchange fields.Comment: 26 pages, 6 figure

Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography

Skeletal muscle operates as a near-constant volume system; as such muscle shortening during contraction is transversely linked to radial deformation. Therefore, to assess contractile properties of skeletal muscle, radial displacement can be evoked and measured. Mechanomyography measures muscle radial displacement and during the last 20 years, tensiomyography has become the most commonly used and widely reported technique among the various methodologies of mechanomyography. Tensiomyography has been demonstrated to reliably measure peak radial displacement during evoked muscle twitch, as well as muscle twitch speed. A number of parameters can be extracted from the tensiomyography displacement/time curve and the most commonly used and reliable appear to be peak radial displacement and contraction time. The latter has been described as a valid non-invasive means of characterising skeletal muscle, based on fibre-type composition. Over recent years, applications of tensiomyography measurement within sport and exercise have appeared, with applications relating to injury, recovery and performance. Within the present review, we evaluate the perceived strengths and weaknesses of tensiomyography with regard to its efficacy within applied sports medicine settings. We also highlight future tensiomyography areas that require further investigation. Therefore, the purpose of this review is to critically examine the existing evidence surrounding tensiomyography as a tool within the field of sports medicine

Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Computer-aided lead optimization derives a unique, orally bioavailable inhibitor of the signal transducer and activator of transcription (Stat)3 Src homology 2 domain. BP-1-102 binds Stat3 with an affinity (KD) of 504 nM, blocks Stat3–phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4–6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent tumor cells. BP-1-102–mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8, which is identified as a Stat3 target gene that promotes Stat3-mediated breast tumor cell migration and invasion. Treatment of breast cancer cells with BP-1-102 further blocks Stat3–NF-κB cross-talk, the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule 1, macrophage migration-inhibitory factor/glycosylation-inhibiting factor, interleukin 1 receptor antagonist, and serine protease inhibitor protein 1, and the phosphorylation of focal adhesion kinase and paxillin, while enhancing E-cadherin expression. Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of human breast and lung tumor xenografts