Supplementary Figure 4 from Fer Protein-Tyrosine Kinase Promotes Lung Adenocarcinoma Cell Invasion and Tumor Metastasis
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<p>PDF file - 120K, Fer promotes migration and invasion of A549 cells.</p>Infectivity
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Tyrosine kinase receptors are expressed on the surface of tumor and/or endothelial cells and represent attractive targets for new anti-cancer treatment strategies. The so-called "small molecule" tyrosine kinase inhibitors have been designed to interact with the intracellular ATP binding site of these receptors, subsequently causing arrest of tumor cell proliferation, as well as induction of apoptosis and tumor migration. Furthermore, these molecules can impact on tumor angiogenesis. Tyrosine kinase inhibitors have been evaluated in several clinical trials for various adult malignant tumor entities and are currently being studied in pediatric solid malignancies. In this review, we will address the data available supporting the potential use of tyrosine kinase inhibitors in solid malignancies of childhood. Keywords: Tyrosine kinase, tyrosine kinase inhibitors, imatinib, gefitinib, erlotinib, embryonic tumors, sarcomas, pediatric oncology
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In a soil bioassay, adult Deroceras reticulatum (Stylommatophora: Limacidae) and three different weight-classes of young Arion lusitanicus (Stylommatophora: Arionidae) were exposed to a single dosage (170 dauer larvae per g of soil) of the nematode Phasmarhabditis hermaphrodita monoxenically associated with the bacterium Moraxella osloensis. Groups of 10 slugs were continuously exposed to nematodes for 4 days, and then transferred individually to Petri-dishes containing a disc of Chinese cabbage as food. Food consumption—measured by image analysis—and slug mortality were recorded daily for 10 days. Food consumption was inhibited in both slug species tested. D. reticulatum stopped feeding 6 days after the start of nematode treatment, while all A. lusitanicus continued to feed. However, in the three weight-classes of A. lusitanicus (0.15 g, 0.24 g, 0.45 g), food consumption was reduced by at least 50 %. The greatest reduction in feeding, nearly 90 %, was noted in the smallest A. lusitanicus. The nematodes successfully killed D. reticulatum but were less efficient at killing young A. lusitanicus. At the end of the experiment, mortality was highest in D. reticultatum (98 %) and the smallest weight-class of A. lusitanicus (47 %). There was almost no mortality in the largest weight-class of A. lusitanicus treated with nematodes. P. hermaphrodita associated with M. osloensis can thus be considered as a biological control agent for young stages of A. lusitanicus for its effect as a feeding inhibitor, rather than for its ability to kill the slugs.
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In response to DNA damage, p53 undergoes post-translational modifications (including acetylation) that are critical for its transcriptional activity. However, the mechanism by which p53 acetylation is regulated is still unclear. Here, we describe an essential role for HLA-B-associated transcript 3 (Bat3)/Scythe in controlling the acetylation of p53 required for DNA damage responses. Depletion of Bat3 from human and mouse cells markedly impairs p53-mediated transactivation of its target genes Puma and p21 . Although DNA damage-induced phosphorylation, stabilization, and nuclear accumulation of p53 are not significantly affected by Bat3 depletion, p53 acetylation is almost completely abolished. Bat3 forms a complex with p300, and an increased amount of Bat3 enhances the recruitment of p53 to p300 and facilitates subsequent p53 acetylation. In contrast, Bat3-depleted cells show reduced p53–p300 complex formation and decreased p53 acetylation. Furthermore, consistent with our in vitro findings, thymocytes from Bat3-deficient mice exhibit reduced induction of puma and p21, and are resistant to DNA damage-induced apoptosis in vivo. Our data indicate that Bat3 is a novel and essential regulator of p53-mediated responses to genotoxic stress, and that Bat3 controls DNA damage-induced acetylation of p53.
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In the present study, several multivariate analyses were carried out to assess the taxonomic relationships among European species of the genus Anthoxanthum. A total of 1787 Anthoxanthum specimens representing all European taxa were analyzed. Thirty macro-morphological (13 quantitative and 17 qualitative) and 29 micro-morphological (7 quantitative and 22 qualitative) characters were considered. First, resemblances between specimens were established independently for macro- and micro-morphological characters using Gower's similarity coefficient, and were represented by means of principal coordinates and cluster analyses. Subsequently, different multivariate analyses were applied to quantitative and qualitative macromorphological data to determine the most discriminant characters and the accuracy of the present taxonomic structure of the genus. Finally, dissimilarities among groups of individuals -species and populations- were estimated using the information radius measure and then represented in different dendrograms. Within annuals, Anthoxanthum gracile is clearly differentiated morphologically, yet no compelling morphological differentiation can be found between Anthoxanthum aristatum and Anthoxanthum ovatum. Moreover, the definition of subspecies in the annual taxa is not supported by our results. Then, within perennials, although the morphological relationships among Anthoxanthum amarum, Anthoxanthum odoratum and Anthoxanthum alpinum have also been resolved, further research is needed to assess the taxonomic position of the Macaronesian endemic Anthoxanthum maderense.
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Targeted molecular therapies against the EGF-receptor are novel, promising and potentially radio sensitizing therapeutic approaches in the treatment of glioblastoma (GBM), a highly malignant and treatment refractory brain tumor. As specific EGFR-inhibition rendered up to date only disappointing clinical results, the aim of the present study was to evaluate bispecific EGFR/ErbB2-inhibition.
GBM-cell lines with different co-expression levels of EGFR and ErbB2-receptor were treated with specific EGFR- and bispecific EGFR/ErbB2 tyrosine kinase inhibitors (TKIs) and experimental radiotherapy.
The results underline the importance of the ErbB2-receptor for GBM cells and the potential clinical importance of bispecific EGFR/ErbB2-tyrosine kinase inhibitors, as EGFR/ErbB2-TKIs overcame cellular resistance against specific EGFR-TKIs and showed radio sensitizing properties.
EGFR Inhibitors
Targeted Therapy
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Holcus lanatus
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SUMMARY A hitherto unrecorded virus having flexible rod‐shaped particles about 740–760 × 13 nm was isolated from Anthoxanthum odoratwn L. It was transmitted by sap inoculation, but not by several species of insect, seed or soil to 18 species of Gramineae including wheat, oats and barley. In susceptible species the virus normally produced a mosaic mottling of the leaves which was sometimes followed by a necrotic streaking or striping.
Mosaic virus
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HLA-B-associated transcript 3 (BAT3) was originally identified as one of the genes located within human major histocompatibility complex. It encodes a large proline-rich protein with unknown function. In this study, we found that a fragment of the BAT3 gene product interacts with a candidate tumor suppressor, DAN, in the yeast-based two-hybrid system. We cloned the full-length rat BAT3 cDNA from a fibroblast 3Y1 cDNA library. Our sequence analysis has demonstrated that rat BAT3 cDNA is 3617 nucleotides in length and encodes a full-length BAT3 (1098 amino acids) with an estimated molecular mass of 114,801 daltons, which displays an 87.4% identity with human BAT3. The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3. Green fluorescent protein-tagged BAT3 was largely localized in the cytoplasm of COS cells. Northern hybridization showed that BAT3 mRNA was expressed in all the adult rat tissues examined but predominantly in testis. In addition, the level of BAT3 mRNA expression was more downregulated in some of the transformed cells, including v-mos- and v-Ha-ras-transformed 3Y1 cells, than in the parental cells.
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