Anna Navis - Academia.edu (original) (raw)

Papers by Anna Navis

Journal of Virology, 1994

In a previous study, we have identified endonexin II (E-II) on human liver plasma membranes as a ... more In a previous study, we have identified endonexin II (E-II) on human liver plasma membranes as a specific, Ca(2+)-dependent, small hepatitis B surface antigen (HBsAg)-binding protein. In this article, we describe the spontaneous development of anti-HBs antibodies in rabbits immunized with native or recombinant human liver E-II and in chickens immunized with the F(ab')2 fragment of rabbit anti-human liver E-II immunoglobulin G. Anti-HBs activity was not observed in rabbits immunized with rat liver E-II. Cross-reactivity of anti-E-II antibodies to HBsAg epitopes was excluded, since anti-HBs and anti-E-II activities can be separated by E-II affinity chromatography. The existence of an anti-idiotypic antibody is further demonstrated by competitive binding of human liver E-II and this antibody (Ab2) to small HBsAg, suggesting that Ab2 mimics a specific E-II epitope that interacts with small HBsAg. In addition, it was demonstrated that anti-HBs antibodies developed in rabbits after im...

European Journal of Cancer, 2006

Suppl. Figure 1 consists of 1D NMR spectra (A) and 2D NMR spectra (B) which is demonstrated in 2 ... more Suppl. Figure 1 consists of 1D NMR spectra (A) and 2D NMR spectra (B) which is demonstrated in 2 slides. Suppl. Figure 2 demonstrates the evaluation of proliferation in the glioma xenograft models. Suppl. Figure 3 shows western blot analysis IDH1 and IDH1-R132H proteins in U251 glioma cell lines.

European Journal of Cancer, 2013

European Journal of Cell Biology, 2006

It has long been recognized that interference with the blood supply of a tumour is an effective w... more It has long been recognized that interference with the blood supply of a tumour is an effective way to halt tumour progression, and even induce tumour regression. This can be accomplished by anti-angiogenic treatment which prevents the formation of a tumour neovasculature, or anti-vascular treatment, which aims at destruction of existent tumour vessels. The latter has received relatively little attention because there is a lack of specific tumour-endothelial markers. Instead, the current detailed knowledge on the factors and mechanisms, involved in angiogenesis, has enabled the development of a variety of angiogenesis inhibitors, especially those that target cellular signalling by vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor known. These inhibitors have received lots of attention because they effectively inhibit tumour growth in pre-clinical models. However, in clinical trials these same inhibitors showed very poor anti-tumour activity. In this review we discuss this discrepancy, and we show that the tumour microenvironment is crucial to the sensitivity of tumours to anti-angiogenic therapy.

Molecular pathological characteristics of glioma samples used in this study. (PDF 309Â kb)

HEK293FT cells expressing lentiviral constructs for DUSP26 and PTPRT. (PDF 192Â kb)

Î Î Ct values of 2nd cohort of diffuse glioma samples run for 36 validated primer sets judged as ... more Î Î Ct values of 2nd cohort of diffuse glioma samples run for 36 validated primer sets judged as candidates in the 1st cohort. (PDF 470Â kb)

Immunohistochemical staining for PTPRT on formalin-fixed paraffin-embedded materials. (PDF 303Â kb)

Annals of Surgical Oncology, 2016

Background. In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described.... more Background. In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described. Also, b-catenin, a cyclin D1 regulator, is often overexpressed. Additionally, studies have shown that the t(X;18) translocation influences tumor behavior partly through cyclin D1 activation. We investigated how alterations in the cyclin D1-CDK4/6-Rb axis impact prognosis and studied effects of targeting this axis with the CDK4/6 inhibitor palbociclib. Methods. Synovial sarcoma samples (n = 43) were immunohistochemically stained for b-catenin, cyclin D1, p16, p21, p27, Rb, and phospho-Rb. Fluorescent in situ hybridization (FISH) was performed to detect CCND1 amplification or translocation. In 4 synovial sarcoma cell lines sensitivity to palbociclib was investigated using cell viability assays, and effects on the sensitive cell lines were evaluated on protein level and by cell cycle arrest.

Macromolecular Bioscience, 2013

Targeted carrier systems (e.g., liposomes or nanoparticles) are used to specifically deliver drug... more Targeted carrier systems (e.g., liposomes or nanoparticles) are used to specifically deliver drugs to a site of interest. Site-direction can be achieved by attachment of targeting molecules, such as peptides, DNA/RNA, or antibodies, to the surface of the carrier. Here, the formation of polymersomes with tumor-targeting potential is described. A single-domain antibody (A12) that specifically targets PlexinD1 (a transmembrane protein overexpressed in tumor vasculature) is equipped with an azide-functionality using expressed protein ligation. This azide-containing A12 can subsequently be attached to BCN-functionalized polymersomes using a strain-promoted azide alkyne cycloaddition, thereby forming polymersomes with tumor-targeting potential.

Î Î Ct values of 1st cohort of diffuse glioma samples run for 91 validated primer sets. (PDF 490Â... more Î Î Ct values of 1st cohort of diffuse glioma samples run for 91 validated primer sets. (PDF 490Â kb)

Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF... more Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In in vitro cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, conc...

The Journal of Pathology, 2009

Tumour metastasis is the result of a complex sequence of events, including migration of tumour ce... more Tumour metastasis is the result of a complex sequence of events, including migration of tumour cells through stroma, proteolytic degradation of stromal and vessel wall elements, intravasation, transport through the circulation, extravasation and outgrowth at compatible sites in the body (the 'seed and soil' hypothesis). However, the high incidence of metastasis from various tumour types in liver and lung may be explained by a stochastic process as well, based on the anatomical relationship of the primary tumour with the circulation and mechanical entrapment of metastatic tumour cells in capillary beds. We previously reported that constitutive VEGF-A expression in tumour xenografts facilitates this type of metastatic seeding by promoting shedding of multicellular tumour tissue fragments, surrounded by vessel wall elements, into the circulation. After transport through the vena cava, such fragments may be trapped in pulmonary arteries, allowing them to expand to symptomatic lesions. Here we tested whether this process has clinical relevance for clear cell renal cell carcinoma (ccRCC), a prototype tumour in the sense of high constitutive VEGF-A expression. To this end we collected and analysed outflow samples from the renal vein, directly after tumour nephrectomy, in 42 patients diagnosed with ccRCC. Tumour fragments in venous outflow were observed in 33% of ccRCC patients and correlated with the synchronous presence or metachronous development of pulmonary metastases (p < 0.001, Fisher's exact test). In patients with tumours that, in retrospect, were not of the VEGF-A-expressing clear cell type, tumour fragments were never observed in the renal outflow. These data suggest that, in ccRCC, a VEGF-A-induced phenotype promotes a release of tumour cell clusters into the circulation that may contribute to pulmonary metastasis.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2010

ABSTRACT

Currently available compounds that interfere with VEGF-A signaling effectively inhibit angiogenes... more Currently available compounds that interfere with VEGF-A signaling effectively inhibit angiogenesis in gliomas, but influence diffuse infiltrative growth to a much lesser extent. Development of a functional tumor vascular bed not only involves VEGF-A but also requires platelet derived growth factor receptor-β (PDGFRβ), which induces maturation of tumor blood vessels. Therefore, we tested whether combined inhibition of VEGFR and PDGFRβ increases therapeutic benefit in the orthotopic glioma xenograft models E98 and E473, both displaying the diffuse infiltrative growth that is characteristically observed in most human gliomas. We used bevacizumab and vandetanib as VEGF(R)-inhibitors, and sunitinib to additionally target PDGFRβ. We show that combination therapy of sunitinib and vandetanib does not improve therapeutic efficacy compared to treatment with sunitinib, vandetanib or bevacizumab alone. Furthermore, all compounds induced reduction of vessel leakage in compact E98 tumor areas, resulting in decreased detectability of these mostly infiltrative xenografts in Gd-DTPA enhanced MRI-scans. These data show that inhibition of VEGF signaling cannot be optimized by additional PDGFR inhibition and supports the concept that diffuse infiltrative areas in gliomas are resistant to anti-angiogenic therapy.

Neuro-Oncology

NEURO-ONCOLOGY • MAY 2017 aimed to evaluate therapeutic responses and working mechanisms of dual ... more NEURO-ONCOLOGY • MAY 2017 aimed to evaluate therapeutic responses and working mechanisms of dual inhibition of ALDH and OxPhos in glioblastoma (GBM). MATERIALS AND METHODS: Effect of combined treatment of KN817 and phenformin on GBM tumorspheres (TSs) were evaluated by functional and molecular studies. RESULTS: We found that combined treatment of gossypol and phenformin also reduces ATP level and cell viability in GBM TSs. Gossypol treatment alone or in combination with phenformin significantly reduced expression of stemness factors such as Nestin, Sox2, PDPN, and Oct3/4, and mesenchymal transition-or invasiveness-associated genes including β-catenin, Snail, and Zeb1 in GBM TSs. Functional studies revealed that stemness and invasion were also reduced by combined treatment of gossypol and phenformin. Malate treatment reversed and knockdown of ALDH isoforms mimics these results, suggesting that disruption of ALDH-mediated ATP production is a key working mechanism. In vivo efficacy was examined in an orthotopic mouse xenograft model. Preclinical mouse model confirmed a remarkable therapeutic response to the combined treatment of gossypol and phenformin. CONCLUSION: Our approach demonstrates dual inhibition of tumor bioenergetics, proposing a novel strategy for the treatment of GBM.