Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 2175 patients seen over the last three years in a non-specialized department of internal medicine with no intensive care unit, 100 had supranormal serum lactic dehydrogenase activities. These patients' case-reports have been analyzed. Nearly half the patients (47/100) had a malignant disease (cancer or hemopathy). Among the remaining patients, 19 had a hepatic disorder (alcohol hepatitis in 10, viral hepatitis in 8, and isoniazide hepatitis in 1), 7 had a heart disease (heart failure with hepatomegaly in 5, myocardial infarction in 2), and 27 had various other conditions (including hemolysis in 6 and polymyositis en 3). The value of serum LDH assay is obvious in situations other than acute conditions such as myocardial infarction of pulmonary embolism; these are better known and have not been studied here as their prevalence was low among the patients enlisted in our study. In comparison to other enzymes (alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), transaminases (GOT, GPT) that were also routinely assayed in our patients, abnormal serum LDH activities are much less common and their significance is quite different. An increase in serum and their significance is quite different. An increase in serum LDH activity indicates a serious condition, often with a fatal outcome. The "various other conditions" group includes patients with hemolysis, hepatitis and myositis; the other patients in this group either had severe infectious diseases or died suddenly in the first few days of their hospitalization before diagnosis had been established. Each etiologic group has been analyzed to asses the characteristics of patients with increased LDH activity according to each etiology. Analysis of coincident abnormalities of the other enzymes listed above shows marked differences between etiologic groups; diagnostic accuracy can thus be enhanced in certain conditions. Most patients with malignancies had poorly differentiated tumors, with metastases: 28 had an epithelial tumor, with hepatic and/or bone metastases in 23 cases, 5 had cancer of the liver, 10 had a malignant hemopathy (2 lymphomas, 5 myeloproliferative syndromes, 3 acute leukemias), and 4 had a sarcoma. Cancer of the lung is the most common malignancy (10 cases) and may be responsible for increased serum LDH activity even in patients without metastases. Serum LDH assay is of value for monitoring the course in patients with initially increased activities as it falls under effective therapy and rises during exacerbations.
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PMID:[Value and diagnostic significance of serum lactic dehydrogenase in internal medicine (author's transl)]. 628 24

Peripheral blood progenitor cells (PBPCs) are increasingly used for autografting after high-dose chemotherapy. One advantage of PBPCs over the use of autologous bone marrow would be a reduced risk of tumor-cell contamination. However, the actual level of tumor cells contaminating PBPC harvests is poorly investigated. It is currently not known whether mobilization of PBPCs might also result in mobilization of tumor cells. We evaluated 358 peripheral blood samples from 46 patients with stage IV or high-risk stage II/III breast cancer, small cell (SCLC) or non-small cell (NSCLC) lung cancer, as well as other advanced malignancies for the detection of epithelial tumor cells. Monoclonal antibodies against acidic and basic cytokeratin components and epithelial antigens (HEA) were used in an alkaline phosphatase-anti-alkaline phosphatase assay with a sensitivity of 1 tumor cell within 4 x 10(5) total cells. Before initiation of PBPC mobilization, circulating tumor cells were detected in 2/7 (29%) patients with stage IV breast cancer and in 2/10 (20%) patients with extensive-disease SCLC, respectively. In these patients, an even higher number of circulating tumor cells was detected after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by granulocyte colony-stimulating factor (G-CSF). This approach has previously been shown to be highly effective in mobilizing PBPCs. In the 42 patients without circulating tumor cells during steady state, tumor cells were mobilized in 9/42 (21%) patients after VIP+G-CSF induced recruitment of PBPCs. The overall incidence of tumor cells varied between 4 and 5,600 per 1.6 x 10(6) mononuclear cells analyzed. All stage IV breast cancer patients and 50% of SCLC patients were found to concomitantly mobilize tumor cells and PBPCs. Kinetic analyses showed two patterns of tumor cell recruitment depending on the presence or absence of bone marrow disease: (1) early after chemotherapy (between days 1 and 7) in patients without marrow infiltration, and (2) between days 9 and 16 in patients with marrow infiltration, ie, within the optimal time period for the collection of PBPCs. We show that there is a high proportion of patients with circulating tumor cells under steady-state conditions, and in addition a substantial risk of concomitant tumor cell recruitment upon mobilization of PBPCs, particularly in stage IV breast cancer patients with bone marrow infiltration. The biologic and clinical significance of this finding is unknown at present.
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PMID:Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. 790 97

The emerging clinical relevance of bone marrow micrometastasis has prompted several investigations, using a variety of immunocytochemical approaches. The present study was designed to evaluate some of the variables affecting the immunocytochemical detection of individual epithelial tumor cells in bone marrow. Using an alkaline phosphatase-antialkaline phosphatase staining technique, we evaluated bone marrow aspirates from 358 patients with primary carcinomas of the breast (n = 150), lung (n = 66), prostate (n = 42), or colorectum (n = 100). Individual tumor cells in cytological preparations were detected with monoclonal antibody (MAb) CK2 to the epithelial cytokeratin component 18 (CK18), which has been validated in extensive clinical studies. In addition, the utility of the broad-spectrum MAb A45-B/B3 was explored in this study. The high specificity of MAbs CK2 and A45-B/B3 was supported by analysis of bone marrow from 75 noncarcinoma control patients and by double-marker analysis with MAbs to mesenchymal marker proteins (CD45 and vimentin). In contrast, MAbs E29 and HMFG1, directed to mucin-like epithelial membrane proteins, cross-reacted with hematopoietic cells in 26.7-42.7% of all samples tested. The majority of the 154 positive samples (43.0%) from cancer patients displayed less than 10 CK18-positive cells per 8 x 10(5) marrow cells analyzed. The detection rate, however, was affected by blood contamination of the aspirate, the number of aspirates analyzed, and the number of marrow cells screened per aspiration site. Comparative immunostaining of bone marrow specimens with MAbs CK2 and A45-B/B3 indicated that downregulation of CK18 in micrometastatic carcinoma cells occurs in about 50% of the 172 samples analyzed, regardless of the primary tumor origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. 753 Jan 32

The myc gene family has been implicated in multiple cell processes including proliferation, differentiation, tumorigenesis, and apoptosis. For its cellular growth promoting function, Myc must heterodimerize with Max. To study the effect of Myc inactivation on the growth and differentiation properties of epithelial tumor cells, we transfected the H-630 human colon cancer cell line with bm-max, a mutant Max protein in which DNA-binding activity has been abolished. Cells expressing high levels of bm-Max grow poorly, and the morphology of both colonies and single cells is altered. Moreover, increased bm-Max expression results in a prolonged G alpha/G1 phase accompanied by induced expression of p21 (WAF1/CIP1), elevated levels of alkaline phosphatase (ALP) activity, and accumulation of large fat granuli within the cells. These distinctive cell characteristics are associated with differentiation processes in numerous malignant cell lines. The results of this study support a model in which sequestering of endogenous Myc and Max proteins into "basic mutant" dimers lacking DNA-binding activity is sufficient both to inhibit proliferation and to induce changes in cell behavior consistent with differentiation.
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PMID:c-Myc inactivation by mutant Max alters growth and morphology of NCI-H-630 colon cancer cells. 884 36