Search results for "growth"
showing 10 items of 5134 documents
Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment r…
2012
Abstract Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared wit…
Abstract B5: A BMP7 variant inhibits angiogenesis in vitro and in vivo in part by downregulating VEGFR2 and FGFR1 expression in endothelial cells.
2013
Abstract Glioblastoma multiforme (GBM), the most aggressive glioma, requires active angiogenesis for growth and survival. Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Previously, we demonstrated the use of a BMP7 variant (BMP7v) to differentiate glioblastoma stem-like cells (GSLCs) and significantly reduce their tumorigenic potential (Tate and Pallini et al. 2012). Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, and its cognate in vivo model, we investigated the role of BMP7v in VEGF, basic FGF (bFGF), tumor-driven a…
Breast cancer genome-wide association studies: there is strength in numbers.
2012
Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-spe…
HGG-03. THE GLYCOSPHINGOLIPIDS METABOLISM IS A NOVEL TARGET IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA
2021
Abstract H3K27M-mutant diffuse midline glioma (H3K27M-mutant DMG) is a rare malignant brain tumour entity in children and adults with a median overall survival of around 12 months. Genomic and proteomic analysis may help to identify new target structures, however not all relevant targets are covered by these analyses. Glycosphingolipids and particularly gangliosides play a major role in brain development and have been involved in the pathology of brain tumours. The conversion of ceramide to glucosylceramide via glucosylceramide synthase (GCS) is one of the first steps in the synthesis of glycosphingolipids. Therefore, targeting GCS will inhibit their synthesis. Here we analysed the glycosph…
STAT5 is crucial to maintain leukemic stem cells in acute myelogenous leukemias induced by MOZ-TIF2.
2012
Abstract MOZ-TIF2 is a leukemogenic fusion oncoprotein that confers self-renewal capability to hematopoietic progenitor cells and induces acute myelogenous leukemia (AML) with long latency in bone marrow transplantation assays. Here, we report that FLT3-ITD transforms hematopoietic cells in cooperation with MOZ-TIF2 in vitro and in vivo. Coexpression of FLT3-ITD confers growth factor independent survival/proliferation, shortens disease latency, and results in an increase in the number of leukemic stem cells (LSC). We show that STAT5, a major effector of aberrant FLT3-ITD signal transduction, is both necessary and sufficient for this cooperative effect. In addition, STAT5 signaling is essent…
Broad-spectrum Cross-resistance to Anticancer Drugs Mediated by Epidermal Growth Factor Receptor
2019
BACKGROUND The oncogenic role of epidermal growth factor receptor (EGFR) has been intensively studied. However, its emerging role in drug resistance has not been fully addressed. MATERIALS AND METHODS This study systematically investigated the correlation of mRNA and protein expression of EGFR, as well as gene amplification and mutations with the log-transformed half-maximal inhibitory concentration (log10IC50) values obtained from the NCI panel of 60 human tumor cell lines against 83 standard anticancer agents and the top 10 natural cytotoxic products previously screened by us. RESULTS EGFR protein expression, rather than other measurements, was most frequently associated with drug respons…
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes
2023
Abstract Background Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called “pre-metastatic niche”. In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the m…
Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life/Death Decisions by Tumor Cells with Potential Clinical Applications
2010
Parathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal- as well as midregion- and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treat…
The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models
2014
Background:Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance.Methods:Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo.Results:Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the co…
Abstract 5379: Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung.
2013
Abstract In spite of the recent advances in cancer genomics, the genetics underlying the development of lung squamous cell carcinomas (SCC) is still poorly understood. Here, we investigated the contribution of the cell polarity-related gene, PARD3, to lung SCC carcinogenesis. First, we tested for PARD3 alterations in lung cancer cell lines from various histopathological types. The analysis confirmed an intragenic deletion at the H157 cells and unveiled biallelic mutations in another cell line. Both cell lines are SCCs, which circumscribed PARD3 alterations to this lung cancer type. Next, we extended the genetic screening, which included the determination of mutations and of intragenic delet…