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The survival of cancer patients suffering from glioblastoma multiforme is limited to just a few months even after treatment with the most advanced techniques. The indefinable borders of glioblastoma cell infiltration into the surrounding healthy tissue prevent complete surgical removal. In addition, genetic mutations, epigenetic modifications and microenvironmental heterogeneity cause resistance to radio- and chemotherapy altogether resulting in a hardly to overcome therapeutic scenario. Therefore, the development of efficient therapeutic strategies to combat these tumors requires a better knowledge of genetic and proteomic alterations as well as the infiltrative behavior of glioblastoma cells and how this can be targeted. Among many cell surface receptors, members of the integrin family are known to regulate glioblastoma cell invasion in concert with extracellular matrix degrading proteases. While preclinical and early clinical trials suggested specific integrin targeting as a promising therapeutic approach, clinical trials failed to deliver improved cure rates up to now. Little is known about glioblastoma cell motility, but switches in invasion modes and adaption to specific microenvironmental cues as a consequence of treatment may maintain tumor cell resistance to therapy. Thus, understanding the molecular basis of integrin and protease function for glioblastoma cell invasion in the context of radiochemotherapy is a pressing issue and may be beneficial for the design of efficient therapeutic approaches. This review article summarizes the latest findings on integrins and extracellular matrix in glioblastoma and adds some perspective thoughts on how this knowledge might be exploited for optimized multimodal therapy approaches. 相似文献
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Daniel M. Lajoie Pamela A. Zobel-Thropp Vlad K. Kumirov Vahe Bandarian Greta J. Binford Matthew H. J. Cordes 《PloS one》2013,8(8)
Venoms of brown spiders in the genus Loxosceles contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These toxins cleave the substrates sphingomyelin and lysophosphatidylcholine in mammalian tissues, releasing the choline head group. The other products of substrate cleavage have previously been reported to be monoester phospholipids, which would result from substrate hydrolysis. Using 31P NMR and mass spectrometry we demonstrate that recombinant toxins, as well as whole venoms from diverse Loxosceles species, exclusively catalyze transphosphatidylation rather than hydrolysis, forming cyclic phosphate products from both major substrates. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation. 相似文献
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Christine Knies Gabriel Bonaterra Katharina Hammerbacher Andrea Cordes Ralf Kinscherf Helmut Rosemeyer 《化学与生物多样性》2015,12(12):1902-1944
A series of nucleolipids, containing one of the β‐D ‐ribonucleosides 5‐fluorouridine, 6‐azauridine, uridine, or 5‐methyluridine were lipophilized, either at the O‐2′,3′‐position and/or at N(3) of the nucleobase with a large variety of hydrophobic residues. The resulting nucleolipids as well as the parent nucleosides and the lipid precursors were investigated in vitro with respect to their antitumor activity towards i) ten human tumor cell lines from the NCI 60 panel and ii) partly against three further tumor cell lines, namely a) human astrocytoma/oligodendro glioma GOs‐3, b) rat malignantneuroectodermal BT4Ca, and c) differentiated human THP‐1 macrophages. Inspection of the dose response curves allows two main conclusions concerning lipid determinants lending the corresponding nucleoside an ameliorated or an acquired antitumor activity: i) introduction of either a symmetrical O‐2′,3′‐nonadecylidene ketal group or introduction of an O‐2′,3′‐ethyl levulinate moiety plus an N(3)‐farnesyl group leads often to nucleolipids with significant cytostatic/cytotoxic properties; ii) for the two canonical and non‐toxic nucleosides uridine and 5‐methyluridine, the condensation with also non‐toxic lipids gives nucleolipids with a pronounced antitumor activity. 相似文献
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A genome survey of Moniliophthora perniciosa gives new insights into Witches' Broom Disease of cacao
Jorge MC Mondego Marcelo F Carazzolle Gustavo GL Costa Eduardo F Formighieri Lucas P Parizzi Johana Rincones Carolina Cotomacci Dirce M Carraro Anderson F Cunha Helaine Carrer Ramon O Vidal Raíssa C Estrela Odalys García Daniela PT Thomazella Bruno V de Oliveira Acássia BL Pires Carolina S Maria Rio Marcos Renato R Araújo Marcos H de Moraes Luis AB Castro Karina P Gramacho Marilda S Gonçalves José P Moura Neto Aristóteles Góes Neto Luciana V Barbosa Mark J Guiltinan Bryan A Bailey Lyndel W Meinhardt Julio CM Cascardo Gonçalo AG Pereira 《BMC genomics》2008,9(1):1-25
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