Search results for "expression profiling"
showing 10 items of 658 documents
Subcutaneous panniculitis-like T-cell lymphoma, lupus erythematosus profundus, and overlapping cases: molecular characterization through the study of…
2021
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic cutaneous lymphoma. Differential diagnosis with lupus erythematosus panniculitis (LEP) can be challenging and overlapping cases have been described. In this study, we investigate whether gene expression profiling may or not identify markers that can be used to improve our understanding of the disease and to make a precise differential diagnosis. SPTCL, LEP, and overlapping cases were analyzed using a customized NanoString platform including 208 genes related to T-cell differentiation, stromal signatures, oncogenes, and tumor suppressor genes. Gene expression unsupervised analysis of the samples differentiated SPTCL f…
Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma
2005
Defects in apoptosis signaling in hepatocytes contribute to tumorigenesis in hepatocellular carcinoma (HCC). In addition, treatment with chemotherapeutic drugs is often ineffective in HCC patients due to the apoptosis resistance of cancer cells. Anti-apoptotic members of the Bcl-2 family, including myeloid cell leukemia-1 (Mcl-1), which regulate intrinsic apoptosis induction at the mito-chondrial level, are often overexpressed in human cancer, and are implicated with disease grade and prognosis. Yet, little is known about the role of Mcl-1 in HCC. In this study, we analyzed the relevance of Mcl-1 expression for the apop-tosis resistance of human HCC. Mcl-1 protein expression was considerabl…
Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis.
2005
V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2; synonyms HER2, NEU) encodes a transmembrane glycoprotein with tyrosine kinase-specific activity that acts as a major switch in different signal-transduction processes. ERBB2 amplification and overexpression have been found in a number of human cancers, including breast, ovary and kidney carcinoma. Our aim was to detect ERBB2-regulated target genes that contribute to its tumorigenic effect on a genomewide scale. The differential gene expression profile of ERBB2-transfected and wild-type mouse fibroblasts was monitored employing DNA microarrays. Regulated expression of selected genes was verified by RT-PCR and validated by West…
ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer
2010
AbstractPurpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis…
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.
2014
Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found…
Abstract A24: Bone marrow hematopoietic adaptation as a sensor of early, pre-invasive, epithelial malignancy
2018
Abstract Tumor development and progression is in part dependent on the ability of bystander cells, mostly of bone marrow (BM) origin, to establish a pro-tumorigenic microenvironment. We hypothesized that signs of the cross-talk between elements of the tumor microenvironment and the BM can be identified in the very early phases of cancer development, being finalized to the instruction of a tumor-promoting hematopoiesis. By integrating in situ BM histopathological and immunophenotypical analyses with flow cytometry and gene expression profiling of hematopoietic populations in a spontaneous mouse model of breast carcinogenesis (MMTV/NeuT) we investigated the occurrence and quality of modificat…
Abstract LB061: On-target peripheral and tumor immune microenvironment modulation in patients treated with lacnotuzumab (anti-CSF1, MCS110) + spartal…
2021
Abstract Background: The CSF-1/CSF-1R (colony-stimulating factor-1) pathway plays a significant role in the tumor microenvironment via regulation of tumor-associated macrophages (TAMs). Lacnotuzumab (MCS110) is a humanized monoclonal antibody against CSF-1. Lacnotuzumab may counteract the tumor suppressive microenvironment induced by CSF-1, potentially enhancing the efficacy of PD-1 inhibition. Methods: MCS110Z2102 is a phase 1b/2 study in cancer patients with advanced malignancies treated by lacnotuzumab combined with the PD-1 inhibitor spartalizumab. Eligible patients with previously treated advanced/metastatic solid tumors received 1, 3, 5, 7.5 and 10 mg/kg intravenous doses of lacnotuzu…
The p53 Tumor Suppressor Network Is a Key Responder to Microenvironmental Components of Chronic Inflammatory Stress
2005
Abstract Activation of the p53 network plays a central role in the inflammatory stress response associated with ulcerative colitis and may modulate cancer risk in patients afflicted with this chronic disease. Here, we describe the gene expression profiles associated with four microenvironmental components of the inflammatory response (NO•, H2O2, DNA replication arrest, and hypoxia) that result in p53 stabilization and activation. Isogenic HCT116 and HCT116 TP53−/− colon cancer cells were exposed to the NO• donor Sper/NO, H2O2, hypoxia, or hydroxyurea, and their mRNA was analyzed using oligonucleotide microarrays. Overall, 1,396 genes changed in a p53-dependent manner (P < 0.001), wit…
AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.
2009
SummaryDysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PI…
Unknown primary tumors
2011
An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarra…