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)

A 21-year-old man who had anaplastic large cell lymphoma (ALCL) of the null-cell type with multiple bone involvement is reported. On admission, he had symptoms of incomplete paraplegia and urinary and rectal incontinence. Workup studies for staging revealed para-aortic lymph node swellings and multiple bone involvement including skull, ribs, left iliac bone, and thoracic/lumbar spine. Because paraplegia was rapidly progressive, a decompression operation was performed. The biopsy specimen obtained from the lumbar spine revealed sheetlike proliferation of anaplastic large cells. These cells were positive for CD30 (Ki-1), EMA, vimentin, and p80NPM/ALK, and negative for CD3, CD20 (L26), and CD45 (LCA). Epstein-Barr virus-encoded small RNAs were not detectable in these cells. Thus, the patient was diagnosed as having ALCL of the null-cell type. He was treated with several courses of combination chemotherapy, and finally with total body irradiation plus high-dose chemotherapy supported by peripheral blood stem cell transplantation. However, soon after the treatment, the lymphoma cells massively infiltrated his bone marrow. He died of lymphoma 8 months after admission.
...
PMID:Anaplastic large-cell lymphoma of null-cell type with multiple bone involvement. 987 67

Our previous studies in the hamster pancreatic cancer model have indicated that pancreatic ductal adenocarcinomas derive not only from ductal/ductular cells but also from islets. To verify the presence of carcinogen-responsive cells within islets, we tested the effect of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) on recently established continuous hamster pancreatic islet culture. Isolated pure pancreatic islets of hamsters were treated in vitro with BOP at a concentration of 0.25 mM three times a week for 19 weeks. Each treatment week was designed as a stage. The growth of these cells, designated KL5B, was compared with untreated cultured islets, designated KL5N. As in our previous study, between 14 and 21 days of culture, exocrine and intermediary cells developed within both KL5N and KL5B islets, which were then replaced by undifferentiated cells. No differences were found in the growth patterns of KL5N and KL5B until stage 4, when KL5B cells showed accelerated cell growth and cell pleomorphism, which increased gradually at later stages of treatment. Anchorage-independent and in vivo growth did not appear until stage 19. Mutation of c-Ki-ras at codon 12 (GGT-->GAT) was detected in KL5B cells but not in KL5N cells. In vivo KL5B cells formed anaplastic invasive cancer with areas of glandular formation, overexpressed TGF-alpha and EGFR, expressed cytokeratin, vimentin, laminin and alpha-1 antitrypsin and reacted strongly with L-phytohemagglutinin and tomato lectin. Some cells within islets are responsive to the carcinogenic effects of BOP. Whether these cells represent islet cell precursors (stem cells) or malignant transdifferentiated islet cells remains to be seen.
...
PMID:Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro. 1006 71

Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.
...
PMID:Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity. 1051

Various polypeptide growth factors are generally considered to be involved in the regulation of the nephrogenic process both after acute renal injury and during renal development. Because platelet-derived growth factor B-chain (PDGF-B) has been reported to be expressed in immature tubulus of the developing kidney, PDGF-B could play a role in the process of tubulogenesis. We examined the expression of PDGF-B and PDGF receptors alpha and beta and their localization in kidneys after ischemia/reperfusion injury. The mRNA expressions of PDGF-B, PDGFR-alpha, and PDGFR-beta were enhanced after injury. In the immunohistochemical analysis and/or in situ hybridization, PDGF-B and PDGFR-alpha, beta were expressed after reperfusion in the S3 segment of the proximal tubuli, where they were not expressed normally. The expressions of proliferating cell nuclear antigen and vimentin were concomitantly observed with PDGF-B and PDGFRs in the tubular cells of injured S3 segment at 48 hours after injury. Next, the inhibition of the PDGF-B/PDGFRs axis with either Trapidil or Ki6896, which was found to inhibit the phosphorylation of PDGFR-beta selectively, resulted in a rise of serum creatinine, higher mortality rate, abnormal regenerating process, and suppressed proliferation of tubular epithelial cells. These findings suggest that the PDGF-B/PDGFRs axis is involved in the proliferation of injured tubular cells and plays an important role in the regeneration of tubular cells from acute ischemic injury.
...
PMID:Role of PDGF B-chain and PDGF receptors in rat tubular regeneration after acute injury. 1055 Mar 25

Platelet-derived growth factor (PDGF) B-chain and PDGF receptor beta (PDGFR beta) are essential for glomerulogenesis. Mice deficient in PDGF B-chain or PDGFR beta exhibit an abnormal glomerular phenotype characterized by total lack of mesangial cells. In this study, we localized PDGFR beta in the developing rat kidney and explored the biological effects of PDGF in metanephric mesenchymal cells in an attempt to determine the mechanism by which PDGF regulates mesangial cell development. Immunohistochemical and in situ hybridization studies of rat embryonic kidneys reveal that PDGFR beta localizes to undifferentiated metanephric mesenchyme and is later expressed in the cleft of the comma-shaped and S-shaped bodies and in more mature glomeruli in a mesangial distribution. We also isolated and characterized cells from rat metanephric mesenchyme. Metanephric mesenchymal cells express vimentin and alpha-smooth muscle actin but not cytokeratin. These cells also express functional PDGFR beta, as demonstrated by autophosphorylation of the receptor as well as activation of phosphatidylinositol 3 kinase in response to PDGF B-chain homodimer. PDGF B-chain also induces migration and proliferation of metanephric mesenchymal cells. Taken together with the fact that PDGF B-chain is expressed in the glomerular epithelium and mesangial area, as demonstrated in the human embryonic kidney, we suggest that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangial area. PDGF B-chain also likely stimulates proliferation of mesangial cell precursors in an autocrine fashion once these cells migrate to the glomerular tuft.
...
PMID:Platelet-derived growth factor receptor beta regulates migration and DNA synthesis in metanephric mesenchymal cells. 1073 1

Permanent glioma cell lines are invaluable tools in understanding the biology of glioblastomas. The present study reports the establishment of a clonal human cell line, GBM6840, derived from a biopsy of paediatric cerebellar glioblastoma multiforme. GBM6840 had a doubling time of 32 h and grew as a monolayer of large round cells that retained immunopositivity for glial fibrillary acidic protein and vimentin. Karyotypic analysis revealed a modal chromosome number of 68 and polysomies of chromosomes 3, 5 and 20, as well as the presence of 3-4 marker chromosomes. GBM6840 also showed anchorage-independent growth in soft agar and tumour formation in nude mice. The p16(CDKN2A) gene was transcriptionally silenced by hypermethylation, consistent with the lack of protein expression observed in the original tumour and cultured cells. Western blot analysis revealed normal protein expression of pRb and CDK4. It appears that p16 is the major component altered in the cell cycle pathway and may confer these cells unrestrained proliferation potential. Neither EGFR gene amplification nor over-expression of the protein was detected in the cultured cells. Over-expression of the p53 protein was observed in the majority of cells, despite undetectable mutation (exons 5-8) in the gene. One allele of the PTEN gene was found to be mutated during in vitro cultivation. Telomerase activity was demonstrated in the cultured cells but not in the original tumour, supporting the hypothesis that telomerase is required for the in vitro immortalization process.
...
PMID:Establishment and characterization of a human cell line from paediatric cerebellar glioblastoma multiforme. 1073 64

A study to compare the immuno-histochemical profile of the human rete ovarii, and epoophoron, with the Fallopian tube and ovarian surface epithelium was performed with 31 antibodies and antisera. A reaction was present in the epithelial cytoplasm of the rete ovarii and epoophoron of mesonephric origin, for vimentin, GFAP, cytokeratin markers, (AE1/AE3, MNF116; Cam 5.2, 34 beta E12 and for the monospecific antibodies to cytokeratins 7 and 19), heat shock protein 27, in the cell membrane for HBME-1, EMA and in the subepithelial collagen for collagen IV. Reactions were present only in the epithelium in the rete ovarii for EGFR (one case) and CA-125 (four cases). A reaction was present in the epithelium of the epoophoron only for Ber-EP-4 and S100. There was no reaction with antibodies for desmin, neurofilament protein, cytokeratins 20 or 14, actin, calretinin, E-cadherin, C-erb-B2, or CEA (monoclonal and polyclonal reagents). The immuno-histochemical profile of the Fallopian tube was consistent with its para-mesonephric origin and that in the ovarian surface epithelium was consistent with a proposed modified mesothelial origin. This study provides an immunohistochemical profile of these structures with a large panel of commonly available antibodies and antisera, confirming and extending the findings described in previous studies.
...
PMID:An immunohistochemical study of the rete ovarii and epoophoron. 1084 Aug 24

In normal development, embryonic astrocytes progress through their cell lineage by acquiring differentiation, by apoptosis, and by proliferation. In this study, we show that embryonic astrocytes may maintain and make gains in differentiation as they simultaneously progress through one cell cycle when induced by prolactin (PRL). Prolactin induced the majority of astrocytes to incorporate bromodeoxyuridine (BrdU) with a four-fold increase over controls after 18 h of exposure. Investigating possible mitogenic signaling pathways we show for the first time that prolactin is coupled to a sustained phospholipase D (PLD) activation, with an efficacy similar to the phorbol ester and astrocytic mitogen 12-tetradecanoylphorbol-13-acetate (TPA). Both cyclosporine and suramin abolished this activation. Staurosporine and calphostin C also inhibited the PRL effect by 50%, consistent with involvement of protein kinase C-(PKC)-alpha, the major PKC isoform in astrocytes. Genistein and PP1 blocked the activation indicating additional regulation by cytosolic tyrosine kinases. This profile of PLD activation was suggestive of a PLD I isoform and a mitogenic response. Upon completion of the cell cycle, analysis of glia fibrillary acidic protein (GFAP) and vimentin abundance, and glutamine synthetase (GS) activity showed that astrocytes had gained in expression of differentiation markers. Moreover, the intensity of GFAP immunofluorescence was greater per cell, as was the length of the cell processes. In exploring the signaling for prolactin-induced differentiation we found that prolactin activated the tyrosine kinase Janus kinase (JAK) 2 and significantly stimulated tyrosine, phosphorylation of the prolactin receptor. Stat 1 and 3 were also activated presumably downstream to JAK2 activation. A rapid translocation of the cytosolic Stats over the nucleus was seen in nearly every astrocyte corresponding well with the gains in GFAP per cell. The Stats translocation did not depend on MEK-ERK inhibition by PD98059, inhibition of p38 by 1 microm SB203580, or Src kinase family inhibition by PP1. Our results demonstrate the ability of PRL to concurrently induce activation of PLD, a mitogenic signaling pathway in astrocytes, and prolonged stimulation of Stat1, compatible with the increased GFAP upregulation and cell differentiation. Considered together this data may provide an explanation on the fast gain in both numbers and differentiation in the astrocytic population during development (HD 09402, CRF).
...
PMID:Prolactin concurrently activates src-PLD and JAK/Stat signaling pathways to induce proliferation while promoting differentiation in embryonic astrocytes. 1097 48

The transition of arterial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype may play an essential role in the formation of atherosclerotic and restenotic lesions. This process includes a prominent structural reorganization and allows cells to acquire the ability to migrate, proliferate, and secrete extracellular matrix components. According to Western blotting analysis and immunohistochemical and morphological observations, laminin not only retains SMCs in a contractile state but also possibly stimulates cells to transform a synthetic to a contractile phenotype at an early stage, mediated by P38 MAPK signal transduction. However, fibronectin promotes SMCs to transform from a contractile to a synthetic phenotype, mediated by the ERK MAPK signal pathway. The localization of smooth muscle alpha -actin, myosin heavy chain isoform SM2, and vimentin in explant-isolated rat SMCs was affected by a substrate of fibronectin and laminin and also by ERK MAP kinase inhibitor (PD098059) and P38 MAPK inhibitor (SB203580). Furthermore, vimentin may play a much more important role in differentiation than desmin in phenotype modulation in rat aortic smooth muscle cells.
...
PMID:Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro. 1100 58

A subset of blood cells from patients with B-cell chronic lymphocytic leukemia (CLL) spontaneously differentiates in vitro into large, round, or fibroblast-like adherent cells that display stromal cell markers, namely vimentin and STRO-1. These cells also express stromal cell-derived factor-1 (SDF-1), a CXC chemokine that ordinarily is secreted by marrow stromal cells. Leukemia B cells attach to these blood-derived adherent cells, down-modulate their receptors for SDF-1 (CXCR4), and are protected from undergoing spontaneous apoptosis in vitro. Neutralizing antibodies to SDF-1 inhibit this effect. Moreover, the rapid deterioration in the survival of CLL B cells, when separated from such cells, is mitigated by exogenous SDF-1. This chemokine also results in the rapid down-modulation of CXCR4 and activation of p44/42 mitogen-activated protein-kinase (ERK 1/2) by CLL B cells in vitro. It is concluded that the blood of patients with CLL contains cells that can differentiate into adherent nurse-like cells that protect leukemia cells from undergoing spontaneous apoptosis through an SDF-1-dependent mechanism. In addition to its recently recognized role in CLL B-cell migration, SDF-1-mediated CLL B-cell activation has to be considered a new mechanism involved in the microenvironmental regulation of CLL B-cell survival. (Blood. 2000;96:2655-2663)
...
PMID:Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. 1102 95


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

---