Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption-ionization-mass spectrometry imaging (MALDI-MSI).

Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids directly involved as potential biomarkers. These biomarkers may be used to determine whether an in vivo wound is going to heal for example if infected. An in vitro LSE model was wounded with a scalpel blade and assessed at day 4 post wounding by histology and MALDI-MSI. Samples were sectioned at wound site and were either formalin fixed paraffin embedded (FFPE) for histology or snapped frozen (FF) for MSI analysis. The combination of using an in vitro wounded skin model with MSI allowed the identification of lipids involved in the skin barrier repair/wound healing process. The technique was able to highlight lipids directly in the wound site and distinguish differences in lipid distribution between the epidermis and wound site. This novel method of coupling an in vitro LSE with MSI allowed in depth molecular analysis of the skin barrier repair/wound healing process. The technique allowed the identification of lipids directly involved in the skin barrier repair/wound healing process, indicating these biomarkers may be potentially be used within clinic. These biomarkers will help determine, which stage of the skin barrier repair/wound healing process the wound is in to provide the best treatment. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

There is a clinical need for reliable biomarkers for lung cancer that permit early diagnosis of the disease and provide prediction of histological phenotype. A prospective study design was used with a study population of patients with suspected lung cancer. Blood samples were collected from 17 patients with histologically confirmed squamous cell lung carcinoma, 17 individuals with adenocarcinoma, and 17 control individuals who did not subsequently have a diagnosis of lung cancer or any other cancer. Blood plasma samples were analysed for their lipid profiles using liquid chromatography coupled with high resolution mass spectrometry. Data were analysed using multivariate statistical methods. There was good separation between histological subtypes and control groups and also between individuals with a subsequent diagnosis of adenocarcinoma and squamous cell carcinoma (sensitivity 80 %, specificity 83 %, Q2 = 0.70). Alterations in the levels of different classes of lipids including triglycerides (TGs), phosphatidylinositols (PIs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), free fatty acids, lysophospholipids and sphingolipids were observed in squamous carcinoma and adenocarcinoma lung cancer patients when compared with control patients. In conclusion, this study has identified candidate lipid biomarkers of non-small cell lung cancer patients which may be helpful to indicate the tumour subtype and to differentiate them from patients who do not have lung cancer. Measuring these biomarkers has the potential to improve diagnosis in patients with suspected lung cancer and risk stratification in screening

Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

10.1371/journal.pone.0057015PLoS ONE83

A obrigação alimentar dos parentes por afinidade

A presente monografia visa analisar a obrigação alimentar dos parentes por afinidade, levando-se em consideração a existência da relação socioafetiva entre padrasto/madrasta e enteado/enteada. Inicialmente, ter-se-á uma visão histórica da concepção de família, os princípios constitucionais norteadores do Direito de Família, assim como as formas de reconhecimento de filiação, com ênfase na socioafetiva. Ato contínuo abordar-se-á o instituto jurídico dos “alimentos” a sua conceituação, natureza jurídica, titularidade (ativa e passiva) e repercussões. Descrever-se-á sobre o parentesco e suas modalidades bem como as respectivas classificações, aduzir-se-á acerca de quais modalidades de parentesco geram a obrigação alimentar, optando-se pelo defendido pelos vanguardistas, quanto à possibilidade do parentesco por afinidade também originar esta responsabilidade, todavia, de forma subsidiária e complementar ao dever alimentar dos parentes consanguíneos. Por fim, analisar-se-á julgados que corroboram a tese aqui sustentada, os quais reconhecem tanto a existência da filiação socioafetiva e, por vezes, a sua prevalência até mesmo ao elo biológico, visando atender-se ao melhor interesse da criança, quanto à possibilidade dos padrastos e madrastas terem a obrigação de prestar alimentos aos enteados, tendo em vista o parentesco criado entre eles diante da convivência familiar e o dever de solidariedade entre parentes

Granulocyte-Derived Cationic Peptide Enhances Homing and Engraftment of Bone Marrow Stem Cells after Transplantation

Current strategies to accelerate hematopoietic reconstitution after transplantation include transplantation of greater numbers of hematopoietic stem/progenitor cells (HSPCs) or ex vivo expansion of harvested HSPCs before transplant. However, the number of cells available for transplantation is usually low, and strategies to expand HSPCs and maintain equivalent engraftment capability ex vivo are limited. We noted that activated granulocyte-derived cationic peptides positively primed responsiveness of HSPCs to a CXCL12 gradient. Accordingly, we noted that accelerated homing/engraftment of β-defensin-2, a well-known antimicrobial cationic peptide, primed bone marrow nucleated cells (BMNCs) compared to normal BMNCs after transplantation into lethally irradiated recipients. We envision that small cationic peptides, which primarily possess antimicrobial functions and are harmless to mammalian cells, could be applied to prime HSPCs before transplantation. This novel approach would be particularly important in cord blood transplantation, where the number of HSPCs available for transplantation is usually limited

Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression

<p>Abstract</p> <p>Background</p> <p>Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125–132).</p> <p>Methods</p> <p>The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells.</p> <p>Results</p> <p>Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells.</p> <p>Conclusion</p> <p>Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression <it>in vitro</it>.</p

La evolución es un hecho tan indiscutible como que la Tierra no es plana

Reproducció del document publicat a: https://theconversation.com/la-evolucion-es-un-hecho-tan-indiscutible-como-que-la-tierra-no-es-plana-162135Nos ha sorprendido leer un artículo donde un conocido escritor niega la evolución biológica, ignorando la evidencia científica. No es nuestra intención antagonizar con dicho autor ni discutir uno por uno los muchos errores que contiene su text

Thymoquinone Inhibits Bone Metastasis of Breast Cancer Cells Through Abrogation of the CXCR4 Signaling Axis

Overexpression of chemokine receptor type 4 (CXCR4) has been found to be associated with increased cell proliferation, metastasis and also act as an indicator of poor prognosis in patients with breast cancer. Therefore, new agents that can abrogate CXCR4 expression have potential against breast cancer metastasis. In this study, we examined the potential effect of thymoquinone (TQ), derived from the seeds of Nigella sativa, on the expression and regulation of CXCR4 in breast cancer cells. TQ was found to inhibit the expression of CXCR4 in MDA-MB-231 triple negative breast cancer (TNBC) cells in a dose- and time-dependent manner. It was noted that suppression of CXCR4 by TQ was possibly transcriptionally regulated, as treatment with this drug caused down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and suppression of NF-kB binding to the CXCR4 promoter. Pretreatment with a proteasome inhibitor and/or lysosomal stabilization did not affect TQ induced suppression of CXCR4. Down-regulation of CXCR4 was further correlated with the inhibition of CXCL12-mediated migration and invasion of MDA-MB-231 cells. Interestingly, it was observed that the deletion of p65 could reverse the observed antiinvasive/ anti-migratory effects of TQ in breast cancer cells. TQ also dose-dependently inhibited MDA-MB-231 tumor growth and tumor vascularity in a chick chorioallantoic membrane assay model. We also observed TQ (2 and 4 mg/kg) treatment significantly suppressed multiple lung, brain, and bone metastases in a dose-dependent manner in a metastasis breast cancer mouse model. Interestingly, H&E and immunohistochemical analysis of bone isolated from TQ treated mice indicated a reduction in number of osteolytic lesions and the expression of metastatic biomarkers. In conclusion, the results indicate that TQ primarily exerts its anti-metastatic effects by down-regulation of NF-kB regulated CXCR4 expression and thus has potential for the treatment of breast cancer

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model

INTRODUCTION: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. METHODS: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. RESULTS: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on adhesive substrates (type I collagen, fibronectin and laminin) and induced different responses in small GTPases, such as RhoA and Rac-1 activation, and changes in cell morphology. In addition, binding to various ECM components caused redistribution of chemokine receptors at tumour cell surfaces. In vivo, blocking CXCR4 decreased extravasation of highly metastatic MDA-MB-231 cells (p < 0.05), but initial cell adhesion within the liver sinusoids was not affected. In contrast, the less metastatic MDA-MB-468 cells showed reduced cell adhesion but similar migration within the hepatic microcirculation. CONCLUSION: Chemokine-induced extravasation of breast cancer cells along specific ECM components appears to be an important regulator but not a rate-limiting factor of their metastatic organ colonization.Claudia Wendel, André Hemping-Bovenkerk, Julia Krasnyanska, Sören Torge Mees, Marina Kochetkova, Sandra Stoeppeler and Jörg Haie