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

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunophenotype analysis of 17 childhood medulloblastoma (MED) and supratentorial primitive neuroectodermal tumors (SPNET) was performed on frozen sections using 16 monoclonal antibodies (MoAb) with the biotin-streptavidin alkaline phosphatase immunohistochemical technique. Neuroectodermal associated antigens, reacting with MoAb UJ13/A, UJ127.11, UJ167.11, and UJ223.8 were detected on greater than 10% of the cells in 15 of 17 MED/SPNET. Thy-1 was present on 14 of 17 tumors and absent on two of three SPNET. Neuronal (NF) and glial (GFAP) differentiation markers were evaluated. NF-H was demonstrated in 15 of 17, NF-M in six of 17 and NF-L in one of 17 tumors; GFAP was positive in nine of 17 patients. In nine of 17 MED/SPNET both proteins were present within the same tumor. Common leukocyte antigen was demonstrated on greater than 50% of the cells in four of 14 tumors as were shared tumor/leukocyte markers using monoclonal antibodies Thy-1, PI153/3, UJ308. The most frequent MED immunophenotype analysis was UJ 13/A+, UJ 127.11+, UJ 167.11+, UJ223.8+, PI 153/3+, A2B5+, GFAP+, NF-H+, and CLA-, NF-M-, NF-L-, 215-, 275-, 282.1-. The authors conclude that MED and SPNET are heterogeneous for expression of 16 markers and have similar immunophenotype analysis profiles, supporting the concept of their common, neuroectodermal origin. Common leukocyte antigen on both tumor cells and leukocytes precludes identification of tumor infiltrating leukocytes using monostaining techniques.
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PMID:Immunophenotype profile of childhood medulloblastomas and supratentorial primitive neuroectodermal tumors using 16 monoclonal antibodies. 219 9

The low (NF-L) and middle (NF-M) molecular weight (Mr) neurofilament (NF) subunits are expressed before the high (NF-H) Mr NF subunit in embryonic neurons. Thereafter, NF-M attains its mature state of phosphorylation more rapidly than does NF-H. However, little is known about NF subunit expression during cell division. A rapidly dividing medulloblastoma cell line (D283 MED), therefore, was examined using flow cytometry, immunochemistry, and a large panel of NF subunit-specific polyclonal and monoclonal antibodies. Many of the monoclonal antibodies (MAbs) distinguished NF-H and NF-M in different states of phosphorylation. By flow cytometry, more than 90% of the D283 cells expressed NF-H and NF-M in different states of phosphorylation, and an antiserum specific for the carboxy terminus of NF-L labeled more than 60% of these cells. Furthermore, the fluorescence intensity produced by MAbs that detected phosphorylated versus nonphosphorylated NF-H and/or NF-M epitopes, appropriately decreased or increased, respectively, by preincubating the D283 cells with alkaline phosphatase. In contrast, cell staining with antibodies specific for phosphate-independent NF protein epitopes did not change substantially as a result of enzymatic dephosphorylation. These results agreed closely with those obtained from studies of normal human spinal cord NF extracts. However, NF-H, NF-M, and NF-L were expressed throughout the cell cycle in dual parameter studies of D283 cells labeled with an antibody and propidium iodide. Nevertheless, reductions in the fluorescence intensity produced with most of these antibodies late in the cell cycle suggested that NF proteins may be subject to modifications in their structure or accessibility to antibody probes during different phases of the cell cycle. These data led to the conclusion that NF subunits are expressed throughout the cell cycle in cultured human medulloblastoma cells, but that subtle changes in the immunoreactivity of these proteins occur during cell division.
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PMID:Phosphate-dependent and independent neurofilament protein epitopes are expressed throughout the cell cycle in human medulloblastoma (D283 MED) cells. 247 22

Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally. The skeleton is the most common site of extraneural metastases, but metastases to the bone marrow can also occur. Four cases of medulloblastoma metastatic to the marrow are reported. In addition, 31 cases from the medical literature are reviewed. Clinical features include bone tenderness, cytopenias and elevated serum alkaline phosphatase and lactic dehydrogenase levels. Skeletal involvement, especially of the pelvic bones, is frequently seen radiographically. Weight loss, soft tissue masses and a requirement for blood transfusion are also associated features. Marrow biopsy specimens are characterized by the presence of a small cell tumor often with fibrosis, necrosis and osteoblastic activity. The symptomatic response to chemotherapy is rapid, but chemotherapy resistance appears quickly. Only 1 in 4 cases diagnosed antemortem in this review lived for more than a year. We conclude that marrow aspiration and biopsy are indicated in the evaluation of patients with medulloblastoma and may serve to diagnose the cause of cytopenias, to verify extraneural spread and to provide prognostic information.
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PMID:Medulloblastoma metastatic to the marrow. Report of four cases and review of the literature. 650 96

The expression of the B-chain of platelet-derived growth factor (PDGF) was analyzed in 29 human brain tumors (4 astrocytomas, 7 glioblastomas, 3 medulloblastomas, 3 oligodendrogliomas, 7 meningiomas, and others) using monoclonal antibody after digestion with alkaline phosphatase, and compared with proliferative activities measured by in vivo uptake of bromodeoxyuridine. Medulloblastomas contained the highest amounts of PDGF B-chain, some four to eight times more than that in control brain tissue. The most predominant PDGF molecule of the medulloblastoma was 17 kd. Astrocytomas, glioblastomas, oligodendrogliomas, and meningiomas contained predominantly 30 and/or 22-24 kd molecules. Glioblastoma and meningioma proliferative activities correlated closely to PDGF concentrations, with only a few exceptions. Tumors that contained a high level of PDGF B-chain showed high proliferative activity, while tumors with high proliferative activity did not always contain a high level of PDGF B-chain. Tumors that contain many PDGF B-chains may thus indicate malignancy.
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PMID:Expression of the B-chain of platelet-derived growth factor and proliferative activity of human brain tumors. 768 50

Bone mineral density (BMD) reaches a peak at approximately 30 years of age, and may be influenced by radiotherapy before completion of skeletal maturation. Regional BMD has been measured using dual energy X-Ray absorptiometry (DEXA) in adults following craniospinal irradiation for medulloblastoma between ages 4 and 19 years, receiving doses of 3500-4000 cGy to the brain and spinal cord. Lumbar spine (LS) and was failure to achieve normal adult BMD at both LS and FN, with a mean reduction at LS of 12.1% +/- 2.4% (p < 0.01) and a mean reduction at FN of 14.3% +/- 3.4% (p < 0.01). The mean body mass index (BMI) was also less than that of a standard population (21.8 +/- 1.5), as were mean standing and sitting heights. No relationship was found between reduction in BMD at either site and age at irradiation, time elapsed since irradiation or BMI at time of scanning. Biochemical and endocrine markers including corrected calcium, alkaline phosphatase, sex hormones and IGF-1 were normal in all seven patients. The reduction in BMD outside the irradiated area suggests that indirect factors may be important in this effect.
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PMID:Reduced bone mineral density in long-term survivors of medulloblastoma. 822 Sep 54

The organization of optimal microenvironmental conditions within the developing thymus for lymphatic stem cell migration and their further maturation requires cellular and humoral participation of the neural crest. Recently, the immunophenotypical (IP) heterogeneity of lymphatic cells has become a scientific fact. Monoclonal antibodies (MoABs) produced against the various subpopulations of the reticulo-epithelial cells (RE) demonstrated their heterogeneity. We suggest that with a library of MoABs, raised against normal neuronal tissues, neural tumors, and a medulloblastoma cell line, including UJ13/A, UJ127.11, UJ167.11, UJ223.8, UJ308, J1153, A2B5, 215.D11, 275.G7, 282.1, antineurofilament (NF - med. m.w.), and anti-Thy-1 it is possible to recognize cells of neural crest origin within the postnatal thymic cellular microenvironment. Evidence has been collected concerning such connections between the nervous system and the thymus, such as the production of neuropeptides, oxytocin, and neurophysin by the thymus. Our immunohistochemical study was carried out on quick-frozen sections of human postnatal thymuses removed during open heart surgery, employing an indirect, alkaline phosphatase conjugated streptavidin-biotin technique. The employed MoABs reacted with the subcapsular (outer cortex) thymic nurse cells (TNCs) and with medullary RE cells, in close contact with already mature, immunocompetent T lymphocytes ready to leave the thymic microenvironment and enter the peripheral blood. The thymic medulla's strong immunoreactivity with A2B5, which binds to the GQ ganglioside, is typical for peptide secreting cells often migrated from the neural crest. A2B5+, Thy-1+ IP was demonstrated on the large TNCs. Cortical RE cells showed reactivity with UJ127.11, UJ223.8, and UJ308. Dense expression of neural crest antigens was detected in the Hassall's bodies (HBs) employing MoABs UJ223.8, UJ308, 215.D11, and 275.G7. These results suggest a neural crest origin for TNCs and for 20% to 30% of the cells of thymic microenvironment. The outer (peripheral) part of the HBs contained functionally very active RE cells. These RE cells also expressed antigens characteristic of the neural crest, detectable with MoABs UJ127.11, UJ223.8, UJ308, J1153, 215.D11, 275.G7 and A2B5.
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PMID:Identification of neural crest derived cells within the cellular microenvironment of the human thymus employing a library of monoclonal antibodies raised against neuronal tissues. 872 10

Central nervous system (CNS) tumors are the most common solid neoplasms in children. Medulloblastomas (MEDs) resemble embryonic neuroectodermal stem cells and their immature, uncommitted neuronal and glial progeny. Apoptosis is a basic physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally, disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) receptor (FasR) and programmed or active cell death (PCD) was studied in childhood MEDs with varying stages of malignancy, and cell differentiation features. The majority of neoplastically transformed, neuroectodermal in origin cells, particularly in MEDs, express FasR, whereas normal cells in the CNS do not. FasR is a transmembrane glycoprotein, which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within childhood PNETs/MEDs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with anti-section i FasR antibodies. The resence of FasL has also been detected in childhood glial tumors. Therefore, a spontaneous, cellular immunophenotype (IP) regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood brain tumors during neoplastic growth and progression. During our systematic immunocytochemical screening, we employed formalin fixed, paraffin-wax embedded tissue sections, as well as frozen sections of 34 primary human childhood PNETs/MEDs. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique, modified by us, provided excellent immunocyto-chemical results. A systematic observation of the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"-the highest possible; number of stained neoplastic cells: +3 to +4, between 50% to 90%) of FasR, was detected employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colon epithelium. Certainly, the coexpression of FasR, FasL, and other PCD-related proteins have also been reported in other human malignancies: breast cancer, colorectal carcinomas, large granular lymphocytic leukemia of T or NK cell origin, melanomas, lung, prostate, pancreas, and hepatocellular carcinomas. The coexpression of both FasR and FasL on several neoplastic cell types may represent an effective mechanism for tumor escape of the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching their signal transduction from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) represents a new and exciting immunotherapeutical possibility in the treatment of primary childhood neuroectodermal tumors.
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PMID:Fas (APO-1, CD95) receptor expression and new options for immunotherapy in childhood medulloblastomas. 1065 26

Matrix metalloproteinases (MMP) are a family of zinc-dependent enzymes which degrade various components of the extracellular matrix (ECM) and play an important role in facilitating neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Expression of MMP-2, -3, -9, -10, and -13 was investigated in both spontaneous and xenografted (cells derived from an established cell-line [DAOY#3]) childhood medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed tissue that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found only in the spontaneous MEDs/PNETs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells in the spontaneous cases, and the staining intensity was also the strongest possible (A,B). Focal (surrounding less than 10% of the neoplastically transformed cells) but strong (A,B) immunoreactivity for collagenase-3 (MMP-13) was also only detected in spontaneous MEDs/PNETs, an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates. Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of B and B,C intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed in the spontaneous cases. Staining for MMP-2 was negative in the xenografted MEDs/PNETs. The only positive immunoreactivity in the xenografted MEDs/PNETs was observed in the case of MMP-9, with expression of strong intensity in the ECM surrounding over 90% of the neoplastically transformed xenografted MED/PNET cells (++++; A,B). It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The data presented here suggest that there are significant differences in the pathophysiology of spontaneous and xenografted human neoplasms, which further establishes the already detected limitations of such models in preclinical cancer research.
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PMID:Significant differences in the matrix metalloproteinase expression profiles of spontaneous medulloblastomas/primitive neuroectodermal tumors as compared with their xenografted, established tumor cell line derived counterparts. 1121 45

Survivin is a member of the inhibitor of apoptosis gene family that is expressed in embryonic tissues during human ontogenesis and most human malignancies, but it is not present in the majority of normal adult tissues. Survivin is also a chromosomal passenger protein required for physiological cell divison. Survivin blocks apoptosis, via its BIR domain, by either directly or indirectly blocking the function of the members of the caspase cascade. The expression of this apoptosis inhibitor protein in medulloblastomas (MEDs) was examined for the first time. During the immunohistochemical study, a sensitive, four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results did, in fact, demonstrate the presence of survivin in 10 to 50 per cent of medulloblastoma (MED) cells with medium intensity immunoreactivity (++, B) in this neuroectodermal brain tumor. These results indicate that survivin is probably not only a diagnostic marker, but also an important prognostic marker for MEDs/PNETs and may be useful in the future grading of malignancy in MEDs, much as grading is done today for astrocytomas (ASTRs). Furthermore, the almost exclusive neoplastic expression of survivin will allow development of new antineoplastic, immunotherapeutic strategies.
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PMID:Survivin expression in childhood medulloblastomas: a possible diagnostic and prognostic marker. 1564 11

Overactivation of epidermal growth factor receptor (EGFR) signaling has been recognized as an important step in the pathogenesis and progression of multiple forms of cancer of epithelial origin. Reports regarding EGFR family members in brain tumors are sparse and, thus, the significance of EGFR expression in childhood brain tumors is unclear. In this study, the expression of the EGFR family members was analyzed in 22 medulloblastomas. During the immunohistochemical study, a sensitive, four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results demonstrated the presence of c-erbB-2 (HER-2) and c-erbB-4 (HER-4) in 10 to 50% of the neoplastic cells of high-grade glial tumors with high immunoreactivity, while c-erbB-3 (HER-3) was only detected in less than 10% of the neoplastically-transformed cells. In a follow-up, 70% of children, usually under 4 years of age, with c-erbB-2 (HER-2)-positive MEDs/PNETs, succumbed to the cancer. The Kaplan-Meier estimation revealed a significant correlation between c-erbB-2 expression and survival (p = 0.002), suggesting that c-erbB-2 (HER-2) is probably a prognostic marker for limited survival. Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumor is incurable in about one-third of patients with medulloblastoma, and the current treatment has a detrimental effect on long-term survivors. As such, the results of this study further support the idea that targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of childhood brain tumors. Moreover, c-erbB-2 (HER-2) expression may also be of use in better classifying brain tumors.
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PMID:Epidermal growth factor receptor (EGFR) expression in childhood brain tumors. 1609 49


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