Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to evaluate the association of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, with tumor grade, microvessel density (MVD) and clinical outcome in patients with soft tissue sarcomas (STSs). Tissue specimens of 28 patients with STSs were analyzed immunohistochemically using specific monoclonal antibodies. Tissue samples were obtained prior to any treatment. Half of the STSs exhibited strong expression of VEGF that was associated statistically significantly with high tumor grade. Strong expression of KDR/Flk-1 was detected in only 2 sarcomas. No association was demonstrated between VEGF and KDR/Flk-1 expression. MVD was significantly associated with tumor grade and was higher in sarcomas with strong VEGF expression. Limited data on clinical outcome precluded solid analyses for an association with disease progression. This study provides further evidence on the role of VEGF and MVD in tumor aggressiveness in STSs.
...
PMID:Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in soft tissue sarcomas. 1610 Nov 85

Giant cell tumors (GCTs) of the bone are osteolytic neoplasms with variable degrees of aggressiveness. The aim of this study was the molecular characterization of GCT tissue. We established gene expression profiles and discovered a number of genes that have not been described in GCTs before. RNA was prepared from 7 cryopreserved GCTs (primary tumors n = 5, relapses n = 2) and was hybridized to Affymetrix HG U133A microarrays. Paraffin-embedded samples were used for immunohistochemical validation (primary tumors n = 16, relapses n = 6). Gene ontology revealed that the majority of genes, found to be differentially expressed between primary and recurrent GCTs, were associated with receptor tyrosine kinase activity. We selected one upregulated gene (Claudin 7) and four downregulated genes (CD52, Ephrin A1 receptor, autocrine motility factor receptor [AMFR] and fibroblast growth factor receptor 3 [FGFR3] for further analysis using immunohistochemistry. Immunohistochemical analysis of CD52, AMFR, and Ephrin A1 receptor revealed expression profiles concordant with the microarray data, also with regard to differences between primary tumors and relapses.
...
PMID:Giant cell tumors of the bone: molecular profiling and expression analysis of Ephrin A1 receptor, Claudin 7, CD52, FGFR3 and AMFR. 1632 7

A new diagnostic tool must pass three major tests before it is adopted for routine clinical use. First, the tool must be robust and reproducible; second, the clinical value of the tool must be proven, i.e. the tool should reliably trigger a clinical decision that results in patient benefit; and, third, the clinical community has to be convinced of the need for this tool and the benefits it affords. Another factor that can influence the adoption of new tools relates to the cost and the vagaries of insurance reimbursement. The Cancer Diagnosis Program (CDP) of the US National Cancer Institute (NCI) launched the Program for the Assessment of Clinical Cancer Tests (PACCT) in 2000 to develop a process for moving the results of new technologies and new understanding of cancer biology more efficiently and effectively into clinical practice. PACCT has developed an algorithm that incorporates the iterative nature of assay development into an evaluation process that includes developers and end users. The effective introduction of new tests into clinical practice has been hampered by a series of common problems that are best described using examples of successes and failures. The successful application of the PACCT algorithm is described in the discussion of the recent development of the OncotypeDX assay and plan for a prospective trial of this assay by the NCI-supported Clinical Trials Cooperative Groups. The assay uses reverse transcription (RT)-PCR evaluation of a set of 16 genes that were shown to strongly associate with the risk of recurrence of breast cancer in women who presented with early stage disease (hormone responsive, and no involvement of the auxiliary lymph nodes). The test is highly reproducible. It provides information to aid the physician and patient in making important clinical decisions, including the aggressiveness of the therapy that should be recommended. A trial is planned to test whether OncotypeDX can be used as a standalone trigger for specific treatment decisions. The problems that have been encountered and have delayed the development of other diagnostic tools are exemplified in the development of tests for human epidermal growth factor receptor (HER2) overexpression, for predictors of response to epidermal growth factor receptor inhibitors, and for the detection of residual disease following chemotherapy.
...
PMID:Cancer diagnostics: decision criteria for marker utilization in the clinic. 1633 1

Tissue factor (TF), the primary cellular initiator of blood coagulation, is also involved in cancer-related processes such as hypercoagulability (Trousseau syndrome), tumor growth, angiogenesis, and metastasis. Indeed, elevated TF expression by cancer cells and their associated endothelial cells has been reported frequently. Oncogenic events in cancer cells (e.g., expression of mutant K- ras, EGFR, PTEN or p53) lead to an increase in TF levels and activity, and thereby promote tumor aggressiveness, angiogenesis, and hypercoagulability. Like TF, thrombin receptor (protease-activated receptor-1) is also upregulated in cancer cells expressing oncogenic K -ras. Pharmacological antagonists of some of these transforming genes (e.g., epidermal growth factor receptor inhibitors) could diminish TF expression, both locally and systemically, and hence these targeted agents could be viewed as potential indirect and cancer-specific anticoagulants, in addition to their direct antitumor effects. We postulate that levels of circulating TF may be useful in monitoring the biological activity of these agents. Although TF is essential for vascular development, its expression by tumor-associated endothelium appears to play a subtle and seemingly dispensable role. Thus, TF is a pivotal element of the tumor-vascular interface, is involved in many cancer-related processes, and may well constitute a promising new target for anticancer combination therapies in some disease settings.
...
PMID:Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy. 1647 63

Gastrointestinal stromal tumors (GISTs), the most common nonepithelial neoplasms of the gastrointestinal (GI) tract, occur most commonly in the stomach. These neoplasms were previously classified as smooth muscle tumors, but it has become apparent that they represent distinct clinicopathologic entities. All GISTs should be considered as having malignant potential, although they display varying degrees of aggressiveness. Although usually asymptomatic, large GISTs may present with pain or bleeding. Definitive diagnosis is made by immunohistochemical staining of the tissue for CD117, also known as KIT protein, a cell membrane receptor with tyrosine kinase activity. Size and mitotic activity are predictive of malignant behavior. Primary treatment for GISTs with high malignant potential is surgical resection. Specific therapy targeting the KIT receptor with imatinib has resulted in improved outcomes for patients with unresectable, metastatic, and recurrent disease.
...
PMID:Gastrointestinal stromal tumor (GIST). 1653 79

The aggressiveness of meningiomas is unpredictable. HER2 represents a well-known prognostic factor in various tumors such as breast carcinomas. This work was designed to study HER2 protein expression and HER2 gene amplification in meningiomas and to evaluate their prognostic value. Frozen sections of 35 meningiomas were immunostained for HER2, estrogen receptor, progesterone receptor, E-cadherin, and MIB-1. Meningiomas immunostained for HER2 were further examined for the HER2 gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2-q12. Complete clinical information was obtained in all cases. The study included 15 atypical meningiomas, 3 anaplastic meningiomas, and 17 classic meningiomas. Five atypical/anaplastic meningiomas and 5 classic meningiomas of the whole 35 (28.5%) meningiomas expressed HER2 protein. This was considered as an overexpression in comparison with negative normal meninges. Fluorescence in situ hybridization demonstrated more HER2 gene copy in 4 of these 10 HER2-positive meningiomas. At equivalent histologic grading, meningiomas with HER2 overexpression exhibited similar immunohistochemical parameters of prognostic value than their HER2-negative counterparts; however, the rate of tumor recurrence was significantly higher in meningiomas with HER2 overexpression than in HER2-negative meningiomas. Conversely, HER2 amplification was not associated with recurrence. Some meningiomas exhibit HER2 protein overexpression in part induced by gene amplification. However, only HER2 overexpression could represent an independent prognostic factor in meningiomas.
...
PMID:Prognostic value of HER2 expression in meningiomas: an immunohistochemical and fluorescence in situ hybridization study. 1656 15

The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in higher-grade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P = 0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.
...
PMID:Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer. 1657 3

Oncogenic activation of the receptor tyrosine kinase ERBB2 is a key event in the development of a number of epithelial malignancies. In these tumors, high levels of ERBB2 are strongly associated with metastatic disease and poor prognosis. Paradoxically, an inherent cellular response to hypermitogenic signaling by ERBB2 and other oncogenes seems to be growth arrest, rather than proliferation. Molecular characterization of this yet undefined antiproliferative state in independent cell lines overexpressing either wild-type ERBB2 or the mutationally activated receptor unveiled a dramatic induction of the alpha5beta1 integrin fibronectin receptor. alpha5 Integrin up-regulation is mainly a transcriptional response mediated by the hypoxia-inducible transcription factors (HIF), leading to a massive increase in membrane-resident receptor molecules and enhanced fibronectin adhesiveness of the respective cells. Functionally, ERBB2-dependent ligation of fibronectin results in improved survival of mammary adenocarcinoma cells under adverse conditions, like serum withdrawal, hypoxia, and chemotherapy. HIF-1alpha is an independent predictor of poor overall survival in patients with breast cancer. In particular, HIF-1alpha overexpression correlates significantly with early local relapse and distant metastasis, a phenotype also highly characteristic of ERBB2-positive tumors. As HIF-1alpha is known to be stabilized by ERBB2 signaling under normoxic conditions, we propose that alpha5 integrin is a major effector in this regulatory circuit and may represent the molecular basis for the HIF-1alpha-dependent aggressiveness observed in ERBB2-overexpressing breast carcinomas. Hypermitogenic ERBB2 signaling and tumor hypoxia may act synergistically to favor the establishment of chemoresistant dormant micrometastatic cells frequently observed in patients with breast cancer. This new insight could be the basis for additional approaches complementing current cancer therapy.
...
PMID:ERBB2-mediated transcriptional up-regulation of the alpha5beta1 integrin fibronectin receptor promotes tumor cell survival under adverse conditions. 1658 98

Medullary breast cancer (MBC) is a rare but enigmatic pathologic type of breast cancer. Despite features of aggressiveness, MBC is associated with a favorable prognosis. Morphologic diagnosis remains difficult in many cases. Very little is known about the molecular alterations involved in MBC. Notably, it is not clear whether MBC and ductal breast cancer (DBC) represent molecularly distinct entities and what genes/proteins might account for their differences. Using whole-genome oligonucleotide microarrays, we compared gene expression profiles of 22 MBCs and 44 grade III DBCs. We show that MBCs are less heterogeneous than DBCs. Whereas different molecular subtypes (luminal A, luminal B, basal, ERBB2-overexpressing, and normal-like) exist in DBCs, 95% MBCs display a basal profile, similar to that of basal DBCs. Supervised analysis identified gene expression signatures that discriminated MBCs from DBCs. Discriminator genes are associated with various cellular processes related to MBC features, in particular immune reaction and apoptosis. As compared with MBCs, basal DBCs overexpress genes involved in smooth muscle cell differentiation, suggesting that MBCs are a distinct subgroup of basal breast cancer with limited myoepithelial differentiation. Finally, MBCs overexpress a series of genes located on the 12p13 and 6p21 chromosomal regions known to contain pluripotency genes. Our results contribute to a better understanding of MBC and of mammary oncogenesis in general.
...
PMID:Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. 1665 14

CCAAT/enhancer binding protein beta (C/EBPbeta) is one of a 6-member family of C/EBPs. These transcription factors are involved in the regulation of various aspects of cellular growth and differentiation. Although C/EBPbeta has important functions in B- and T-cell differentiation, its expression has not been well studied in lymphoid tissues. We, therefore, analyzed its expression by immunohistochemistry and Western blot in normal lymphoid tissues and in 248 well-characterized lymphomas and lymphoma cell lines. Nonneoplastic lymphoid tissues and most B-cell, T-cell, and Hodgkin lymphomas lacked detectable levels of C/EBPbeta. In contrast, most (40 of 45; 88%) cases of ALK-positive anaplastic large cell lymphoma (ALCL) strongly expressed C/EBPbeta. Western blot analysis confirmed C/EBPbeta expression in the ALK-positive ALCLs and demonstrated elevated levels of the LIP isoform, which has been associated with increased proliferation and aggressiveness in carcinomas. Transfection of Ba/F3 and 32D cells with NPM-ALK and a kinase-inhibitable modified NPM-ALK resulted in the induction of C/EBPbeta and demonstrated dependence on NPM-ALK kinase activity. In conclusion, we report the constitutive expression of C/EBPbeta in ALK-positive ALCL and show its relationship to NPM-ALK. We suggest that C/EBPbeta is likely to play an important role in the pathogenesis and unique phenotype of this lymphoma.
...
PMID:NPM-ALK-dependent expression of the transcription factor CCAAT/enhancer binding protein beta in ALK-positive anaplastic large cell lymphoma. 1670 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---