Search results for "Process"

Partecipazione, tv e campagna elettorale

2007

Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma.

2001

In cervical carcinomas abnormalities in the MHC class I surface expression are a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP1 thereby resulting in impaired T cell response. In order to understand the role of other components of the MHC class I antigen processing machinery (APM) in the immune escape, 16 surgically removed primary cervical carcinoma lesions were analyzed for their mRNA expression of the heterodimeric peptide transporter TAP, the constitutive and interferon (IFN)-gamma inducible proteasome subunits and their activators PA28alpha/beta, various chaperones as well as MHC class I antigens. High expression levels o…

HLA class I antigen abnormalities and immune escape by malignant cells

2002

Abbreviations used in this paper: APM, antigen processing machinery; β2m,β2 microglobulin; bp, base pair; CTL, cytotoxic T lymphocytes; ER, endoplasmic reticulum; HC, heavy chain; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; KIR, killing inhibitory receptors; LMP, low molecular weight proteins; LOH, loss of heterozygosity; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK, natural killer; PA, proteasome activator; PCR, polymerase chain reaction; RCC, renal cell carcinoma; SCLC, small cell-lung carcinoma; TAA, tumor-associated antigens; TAP, transporter associated with antigen processing; TCR, T cell receptor; TNF, tumor necrosis factor; w…

In human retinoblastoma Y79 cells okadaic acid-parthenolide co-treatment induces synergistic apoptotic effects, with PTEN as a key player.

2013

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. here, we investigated the effects of two natural compounds okadaic acid (OKa) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKa/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-akt levels, increasin…

Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes

2014

International audience; : In addition to their cytoprotective role in stressful conditions, heat shock proteins (HSPs) are involved in specific differentiation pathways, e.g. we have identified a role for HSP90 in macrophage differentiation of human peripheral blood monocytes exposed to Macrophage Colony-Stimulating Factor (M-CSF). Here, we show that deletion of the main transcription factor involved in heat shock gene regulation, heat shock factor 1 (HSF1), affects M-CSF-driven differentiation of mouse bone marrow cells. HSF1 transiently accumulates in the nucleus of human monocytes undergoing macrophage differentiation, including M-CSF-treated peripheral blood monocytes and phorbol ester-…

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…

Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation.

2005

In humans as in other animal species, CD8+ cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus-infected and malignant cell growth. The interactions between CD8+ T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen-derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8+ T-cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell-mediated ly…

XPO1E571K Mutation Modifies Exportin 1 Localisation and Interactome in B-cell Lymphoma

2020

The XPO1 gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) cases harboured a recurrent XPO1 point mutation (NM_003400, chr2:g61718472C&gt

MHC class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma

2003

Colorectal tumorigenesis has been associated with the progressive acquisition of a variety of genetic alterations. These include mutations of the Ki-ras proto-oncogene in codons 12 and 13, which account for 85% of genetic changes in colorectal cancer. In murine in vitro models of oncogenic transformation, an association between ras-mediated transformation and downregulation of different components of the MHC class I antigen processing machinery (APM) has been described. In order to investigate whether this association also exists in human tumors, 10 cases of high-grade intraepithelial neoplasia (HIN), as well as primary tumors and autologous lymph node metastases from 42 patients with color…

MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L

2011

SummaryThe histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-a…