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)

The main objective of this study was to evaluate the safety and efficacy of a perfluorochemical emulsion, Fluosol, with short-term high inspired oxygen tension as an adjuvant to radiation therapy in the treatment of high-grade tumors of the brain. Radiation was delivered to the whole brain at 1.8 Gy per daily treatment for 5 weeks to a total dose of 45 Gy. The radiation portals were then reduced in size to encompass the known volume of tumor, as determined by the presurgical contrast-enhancing ring on computed tomography (CT), plus a 3-cm margin. An additional 10 treatments of 2 Gy each were given to the smaller volume, to bring the total tumor dose to 65 Gy in 7 weeks. This report describes the experience of the first 18 patients treated at the University of Kansas Medical Center on this study, whose median follow-up time from the date of surgery is 77 weeks (62-115 w). Immediately following Fluosol administration on a Monday, patients breathed 100% oxygen for at least 45 minutes prior to and throughout their radiation treatment. On each subsequent day of the weeks in which they received Fluosol, patients breathed 100% oxygen. Hematology and blood chemistries were also drawn prior to Fluosol treatment each Friday during treatment and at the 2-week, 3-month, and 6-month follow-up visits. The median age of the patients was 45 years (16-72); 13 patients were male and 15 carried the diagnosis of glioblastoma multiforme (3 had anaplastic astrocytoma). Two thirds of the patients had an initial allergic reaction to the Fluosol consisting of back pain, shortness of breath, and flushing, but all responded to 50-100 mg of Benadryl. During radiation therapy, all patients developed scalp erythema and complete alopecia by the end of 3 weeks, but no patient required a treatment rest. The serum levels of SGOT, SGPT, and alkaline phosphatase were examined before and throughout the Fluosol treatment and, by week 5, 11/18 of the patients had increased values of all three enzymes above the upper range of normal. These increases persisted through the end of treatment, but most values returned to essentially normal by the 3-month follow-up visit. We conclude that Fluosol, given in the manner described above, appears to be associated with minimal significant side effects and no changes could be detected in the white matter of any of the patients at the time of their magnetic resonance imaging study at 6 months follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A phase I/II study of the use of Fluosol as an adjuvant to radiation therapy in the treatment of primary high-grade brain tumors. 216 56

Precise localization of alkaline phosphatase (ALPase) activity in human gliomas was examined by light and electron microscopy in association with malignant transformation, paying much attention to changes in blood-brain barrier. Materials used were eight cases of gliomas four of which were astrocytoma grade 2, one astrocytoma grade 3, and three, glioblastoma multiforme, respectively. Specimens were quickly fixed in cacodylate-buffered 2% glutaraldehyde at 4 degrees C for 1 hour and rinsed overnight in the same buffer. Frozen or nonfrozen sections (40 microns thick) were made and incubated at 20 degrees C for 40 min, and processed for light and electron microscopy. For the demonstration of ALPase activity, the lead citrate method (Mayahara et al., 1967) was employed. By light microscopy, ALPase activity appeared to be mainly restricted to the capillary wall. By electron microscopy, reaction product representing ALPase activity was distributed in the plasma membrane of endothelial cells both in astrocytomas and in glioblastoma. In astrocytoma grade 2, activity was primarily localized along the abluminal surface of endothelial cells. In glioblastoma, on the other hand, ALPase activity was positive on the luminal surface of the plasma membrane of endothelial cells. It was much more intense than that along the abluminal surface. Regional differences in enzyme cytochemistry may represent functional heterogeneity in the endothelial cell membrane. In brain tumors, changes in distribution pattern of enzyme activity were visualized in the present study in association with glioma malignancy. This might represent a functional aspect of changes in blood-brain barrier in human glioma tissue during course of its malignant transformation.
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PMID:[Alkaline phosphatase activity in human gliomas as revealed by light and electron microscopy]. 304 56

The C6 spheroid implantation glioma model is a simple, easily reproduced model for primary gliomas in which C6 astrocytoma cells are grown in vitro as spheroids and subsequently implanted into the brains of Sprague Dawley rat hosts. This report describes the growth, histology, vessel architecture and vascular permeability of the resulting tumors. The appearance of the tumor was investigated by light and electron microscopy, and by using the alkaline phosphatase technique. The leakage of tracer was measured from vessels in the tumor and peritumoral area at various times during tumor development. The spheroid implant produces a fully vascularized, rapidly growing tumor with many of the characteristics of glioblastoma multiforme, from an avascular focus of neoplastic cells. The major advantage of this model is that the tumors grow in a spheroidal fashion and the tumor-brain interface can be easily located. Many of the important events in the process of vascularization take place at the tumor-brain interface. Two distinctive vascular events appear to occur simultaneously: proliferation of blood vessels and their growth into the tumor mass so that they develop into typical, permeable tumor vessels, and migration of tumor cells along normal vessels into the surrounding brain. Tumor vessels were permeable to the tracer Evans Blue (EB) from the earliest days of ingrowth. Leakage of the EB increased as the tumors increased in size, but eventually leakage plateaued as tumors developed necrotic centers. It is well known that the structural and permeability characteristics of vessels associated with the tumor affect tumor growth. This model will be useful for a number of proposed studies including assessment of various clinical therapies on tumor growth and development, and more specifically, quantitative analysis of the vascularization process in tumors.
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PMID:A new glioma model in rat: the C6 spheroid implantation technique permeability and vascular characterization. 357 71

This study is a quantitative analysis of acid and alkaline phosphatase activity in human brain tumor homogenates and subcellular fractions, in parallel with normal brain tissue. Glioblastoma multiforme, meningioma, astrocytoma and normal tissue samples were separated by ultracentrifugation into five subcellular fractions: nuclei (N), mitochondria (M), microsomes (P), ribosomes (R) and supernatant (S). These two phosphatases showed significant increase in astrocytoma and meningioma tissue homogenates, compared with normal brain tissue. Alkaline phosphatase levels were determined to increase significantly in glioblastoma multiforme tissue homogenates as compared with normals, while those of acid phosphatase were observed to decrease. The results of this investigation also indicate that the subcellular distributions of acid and alkaline phosphatase show differences in the different tumor types. This observation is evidence against metabolic uniformity in tumoral tissue.
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PMID:Acid and alkaline phosphatase activities in homogenates and subcellular fractions of human brain tumors. 407 2

The present study was made to investigate the antinephritic effect of mizoribine in comparison to that of azathioprine by using the nephrotic type of anti-rat glomerular basement membrane rabbit serum (anti-GBM serum)-induced nephritis in rats. The nephrotic type nephritis was induced in rats by two i.v. injections of anti-GBM serum at a 10 day interval. Both drugs were given orally, daily from the 2nd day following the first injection of anti-GBM serum to the 21st day. Mizoribine in doses of 5 and 7.5 mg/kg/day significantly inhibited urinary protein excretion by 30-40% on the 22nd day. Mizoribine at both doses showed an inhibitory tendency on urinary alkaline phosphatase (ALP) excretion on the 9th and 16th days. On the 22nd day, this drug at a dose of 7.5 mg/kg/day inhibited plasma cholesterol (CL) content by 59.6% and wet weight of kidneys by approx. 50%, but no significant difference was seen between the drug-treated and control groups. When renal tissues on the 22nd day were observed under light microscopy, mizoribine at both doses remarkably prevented glomerular changes such as mesangial proliferation and thickening of capillary walls and significantly inhibited the index of glomerular lesions (IGL) by over 60%. On the other hand, azathioprine at a dose of 20 mg/kg/day was as effective as mizoribine at 5 mg/kg/day in inhibiting urinary protein and ALP excretions, plasma CL content and kidney weight. However, azathioprine showed little effect on the IGL. From these results, mizoribine at the dose level of 1/4 to 1/3 of azathioprine showed a more potent effect than azathioprine in this model. Therefore, mizoribine is also expected to have a beneficial effect on nephrotic type nephritis in clinical fields.
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PMID:Studies on antinephritic effect of mizoribine (p-INN, Bredinin), a new immunosuppressive agent, and azathioprine (1) effect on the nephrotic type of anti-GBM nephritis in rats. 662 Jul 26

Apoptosis is a 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 (PCD) death was studied in childhood astrocytomas (ASTRs) with varying stages of malignancy, including pilocytic ASTR, low grade ASTR, anaplastic ASTR, and glioblastoma multiforme (GBM). The great majority of childhood glial tumors, particularly ASTRs express FasR whereas normal cells in the central nervous system (CNS) do not. FasR represents a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within ASTRs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with antibodies developed against FasR. Presence of FasL was also detected in childhood glial tumors. The expression of both FasR and FasL was also observed within the same ASTRs. Therefore, spontaneous, IP regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood glial tumors. During a systematic, immunocytochemical screening of 42 childhood ASTRs tissues divided according to WHO classification: 6 WHO grade I or pilocytic ASTRs; 14 WHO grade II or low grade ASTRs; 16 WHO grade III or anaplastic ASTRs and 6 WHO grade IV or glioblastoma multiforme (GBM), we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: +2 to +4, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR was present on 70% to 90% of tumor cells in pilocytic ASTRs, in 50% to 60% of the tumor cells in low grade ASTRs, in between 30% and 40% of the tumor cells in anaplastic ASTRs, and in between 20% to 35% of GBM cells. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colonic epithelium. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent immunocytochemical results. A broad spectrum of neoplastic cells have been identified to express FasR: 1) carcinomas of epithelial origin, such as breast (ductal invasive, lobular invasive, mucinous), renal cell, gastric, colorectal, endometrial, prostate, pancreas, hepatocellular and large cell and squamous cell lung carcinomas: 2) non-epithelial neoplasms such as B cell mediastinal B cell and nodal non-Hodgkin's lymphomas large granular lymphocytic leukemia of T or NK cell origin malignant fibrous histiocytoma, malignant mesothelioma, leiomyosarcoma, epitheloid sarcoma and alveolar soft part sarcoma, as well as melanomas. Flow cytometry studies have also detected FasR expression on cells of adult T cell, and hairy cell leukemias, as well as in chronic B cell lymphocytic leukemia (BCLL). The coexpression of both FasR and FasL on several malignant cell types may represent an effective mechanism of tumor escape from 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 the signal transduction associated with FasL-FasR coupling from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) may represent a new and exciting type of immunotherapy in the treatment of primary childhood glial tumors.
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PMID:Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? 1058 78

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and local neoplastic cell invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus, crucial in tumor cell invasion and metastasis. The immunocytochemical profile of MMP-2, -3, -9, -10, and -13 expression was observed in 24 primary human childhood astrocytomas (ASTRs) employing an indirect alkaline phosphatase conjugated antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D (negative)]. The two forms of stromelysin, MMP-3 and -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 in ASTRs, 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 (+4) and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using antibodies directed against MMP-2, -9, and -13. Based on these results, MMP-3 and -10 are implicated in the pathogenesis of pediatric ASTRs. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of ASTRs may establish differential regulation and utilization of the various MMPs during the progression of glial tumors, from low-grade pilocytic ASTR to high-grade glioblastoma multiforme.
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PMID:Matrix metalloproteinase expression in childhood astrocytomas. 1106 55

The presence of two proteins of the proline-directed protein kinase (PDPK), the catalytic subunit p34cdc2 and the regulatory subunit p58cyclin A was determined in seven primitive neuroectodermal tumors (PNETs), three choroid plexus neoplasms and eleven astroglial tumors. The highest expression was registered in the cellularly undifferentiated PNETs and glioblastoma multiforme from the astroglial malignant group. Rabbit immunoantiserum against the two subunits of PDPK, a cell proliferation marker, was employed to detect proliferation activity in childhood brain tumors. The PDPK activity was present from Gl- to M-phases in 21 childhood brain tumors with different central nervous system (CNS) localization and cellular atypia. Immunocytochemical analysis employed an indirect, alkaline phosphatase conjugated biotin-streptavidin antigen detection technique on frozen and routine, formalin-fixed and paraffin-wax-embedded tissue sections of brain tumors. We compared the proliferation activity in the cells of normal, morphologically changed and neoplastically transformed choroid plexus. The average proliferation activity was low in comparison with other tissues. The results in normal and neoplastically transformed choroid plexus were very similar. The lowest proliferation activity in the astroglial group belonged to pilocytic ASTRs. The use of cell differentiation as a prognostic factor in primary brain tumors has already been established and is strongly suggested by our research group. Further systematic neoplasm studies and regular employment of these two polyclonal antibodies for immunocytochemical screening experiments are necessary to determine their true diagnostic and prognostic significance.
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PMID:Expression of proline-directed protein kinase, (p34cdc2/p58cyclin A), a novel cell proliferation marker in childhood brain tumors. 1249 5

During the last decade, the aberrant expression of normal testicular proteins in neoplastically transformed cells became common knowledge. Cancer/testis-antigens (CTAs) represent a novel family of immunogenic proteins. The MAGE genes were initially analyzed from melanomas and turned out to have an almost exclusively neoplasm-specific expression pattern. This expression pattern might contribute to the genetic instability of neoplastically transformed cells. In normal adult tissues, most 23 human MAGE genes are expressed only in the testis, but only in the mitotic spermatogonia (germ cells) and in the primary spermatocytes. The immunocytochemistry was carried out on routine, formalin-fixed, paraffin-wax-embedded 3 to 4 mm thick astrocytoma (ASTR) tissue sections. A four step, indirect, biotin-streptavidin based method was employed with alkaline phosphatase enzyme conjugation. Immunocytochemical presence and cellular localization of the MAGE-1 CT-antigen, employing anti-MAGE-1 MoAB was observed only in anaplastic, high-grade ASTRs (100%), certainly including glioblastomas, in this study. The immunoreactivity was always heterogeneous, showing a cytoplasmic pattern and loosely grouped cells with similar staining characteristics being detected within the cellular and hormonal microenvironment of the ASTRs. We never identified MAGE-1, CT-antigen expression in the lowest grade, pilocytic ASTRs. The MAGE-1 CTA expression levels may also be used to evaluate the malignant and dedifferentiation tendencies of low-grade ASTRs and predict the likelihood of mutations of the genome and further dedifferentiation towards even more malignant anaplastic ASTR and glioblastoma multiforme IPs.
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PMID:MAGE-1, a cancer/testis-antigen, expression in childhood astrocytomas as an indicator of tumor progression. 1249 4

Vascular endothelial growth factor (VEGF) is a homodimeric, disulfide-linked glycoprotein which exhibits endothelial cell-specific mitogenic properties. VEGF is also a potent inducer of vascular permeability. There is considerable experimental evidence that VEGF isoforms are strongly involved in provoking neoangiogenesis of neoplastic cells and, consequently, the growth and progression of primary neoplasms (i.e., astrocytic gliomas), including the formation of an invasive and metastatic immunophenotype (IP). During this immunohistochemical study, the presence and tissue localization of VEGF121 was observed in anaplastic, high-grade astrocytomas (AAs) and in glioblastoma multiforme (GBMs) employing the specific monoclonal antibody against it. A sensitive, four-step, alkaline phosphatase-conjugated antigen detection technique was used. The immunoreactivity demonstrated a cytoplasmic, cell surface and extracellular matrix localization pattern in more than 90% of the tumor cells, with high intensity immunoreactivity (++++, A,B) in every high-grade astrocytic glioma tissue. VEGF121 expression was identified mostly within the cytoplasm of tumor cells, suggesting an embryonic, undifferentiated and more malignant cellular IP of high-grade gliomas. Tumor-related neo-angiogenesis and endothelial cell proliferation were also present. The great majority of high-grade astrocytic gliomas are incurable with the three classic therapeutic modalities. In the future, the development of targeted anti-neoplastic treatment strategies, adapted to individual patients, will require molecular identification of the different classes of neoplasm (including subtypes of astrocytomas) according to their stages, biology, prognosis and therapeutic options.
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PMID:Up-regulation of VEGF expression and related neo-angiogenesis in childhood high-grade gliomas: implications for anti-angiogenic anti-neoplastic therapy. 1690 Jul 82


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