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)

Serial carcinoembryonic antigen (CEA) measurements were evaluated in a group of 263 patients undergoing systemic chemotherapy for metastatic colorectal carcinoma. Initial CEA levels were not found to be of value in predicting the likelihood of subsequent tumor response. Although a general relation between serial CEA measurements and clinical tumor measurements was noted, these measurements were discordant in a substantial proportion of patients. Tumor measurements as an index of response to therapy were strongly correlated with survival, whereas changes in CEA values and patient survival were not correlated at a statistically significant level. Serial CEA measurements were perhaps of some value in predicting progression of malignant disease, and were roughly comparable to serum alkaline phosphatase assay in assessing response of liver metastasis to chemotherapy. Overall, serial CEA measurements added little to the standard clinical assessment of patients with advanced colorectal carcinoma receiving chemotherapy.
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PMID:Serial plasma carcinoembryonic antigen measurements in the management of metastatic colorectal carcinoma. 64 45

The presence of the Regan isoenzyme of alkaline phosphatase was demonstrated in the carcinoembryonic antigen-producing human cell line HCT-8 Biochemical, histochemical, immunologic, and electrophoretic methods were used as criteria for the identification and characterization of this isoenzyme.
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PMID:Coproduction of Regan isoenzyme and carcinoembryonic antigen in HCT-8 cells. 81 57

Galactosyltransferase activity was assayed in sera from 58 patients with various types of cancer. On discontinuous polyacrylamide gel electrophoresis a slow-moving peak of galactosyltransferase activity (isoenzyme II) was found to be present in the serum of 43 of these patients in addition to the major isoenzyme I. Isoenzyme II was found in only 2 of 39 patients with various nonmalignant disorders and was not detected in the serum of 22 normal control subjects. There was no correlation between the presence of this electrophoretically distinct isoenzyme and total serum galactosyltransferase activity, alkaline phosphatase, levels of carcinoembryonic antigen, or blood type. However, patients with widespread metastases had significantly higher isoenzyme II levels than those with no metastases or with limited local spread. Further studies will be necessary to evaluate the clinical usefulness of this serum galactosyltransferase isoenzyme in the diagnosis and monitoring of patients with neoplastic disease.
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PMID:Cancer-associated isoenzyme of serum galactosyltransferase. 106 13

Circulating carcinoembryonic antigen (CEA) levels and their relation to liver function test values were studied in 29 jaundiced patients with benign extrahepatic biliary tract obstruction and inflammation. During the obstructive and inflammatory phase, 15 (52%) of the patients had CEA levels greater than 2.5 ng/ml. Elevated CEA levels were associated more frequently with common bile duct stones (and cholangitis) than with gallbladder stones (and cholecystitis) alone, although this difference was not statistically significant. The former often had values greater than 5.0 ng/ml. The highest values were found in two patients with liver abscesses. T'HE CEA levels returned to normal following relief of obstruction in seven of ten patients and increased in two patients who had progressive inflammation. Serum alkaline phosphatase and bilirubin levels were significantly higher in the patients with elevated CEA levels (p smaller than .05). Serum alkaline phosphatase levels showed a significant positive correlation with CEA levels (p smaller than .02). Patients with obstructive jaundice and elevated CEA levels do not necessarily have cancer.
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PMID:Elevated carcinoembryonic antigen levels and biliary tract obstruction. 117 45

We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. We have now developed a "microdot-immunobinding assay" using a specially constructed device to screen efficiently large numbers of patients with nipple discharge for non-palpable breast cancer. The method is as follows: a sample of nipple discharge is placed on a solid phase monoclonal anti-CEA antibody and, if CEA is present in the discharge, it will be detected by a second monoclonal anti-CEA antibody conjugated with alkaline phosphatase. The use of bromochloroindolyl phosphate as a chromogen results in a stable color reaction that can be semiquantitatively analyzed with the naked eye. CEA levels determined by this microdot assay correlated well with those determined using the earlier Elmotec assay. To determine the accuracy of the method, a collaborative study involving 11 institutes in Japan was organized. The CEA levels in nipple discharges from 77 patients undergoing surgery, 44 of whom were diagnosed as having breast cancer, were assayed. The results were that 17 of the 23 patients with palpable breast cancer, and 16 of the 21 patients with non-palpable breast cancer exhibited CEA values > 400 ng/ml, a cut-off value determined in a previous study. The overall accuracy (78%) of this test for diagnosing non-palpable breast cancer was higher than that obtained from ductography or cytology. The system may thus be of use in the screening of early breast cancer.
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PMID:Evaluation of an improved dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge in early breast cancer: results of a multicenter study. 129 55

A new human extrahepatic bile duct carcinoma cell line (KMBC) was established from a serially transplanted tumor in nude mice that originated from a surgically resected tumor from a 73-year-old Japanese man; the cell line has been maintained for 5 five years. KMBC cells proliferate in a monolayered sheet with a population doubling time of 30 hours. Chromosome number was distributed in a range from 37 to 44, with modal numbers of 40 and 41. KMBC cells and the reconstituted tumor in a nude mouse showed moderately to poorly differentiated adenocarcinoma and possessed various functional characteristics of extrahepatic bile duct carcinoma. KMBC cells secreted carbohydrate antigen 19-9, tissue polypeptide antigen, carcinoembryonic antigen, ferritin, beta 2-microglobulin, fibronectin, and alpha 2-macroglobulin and produced glutamic oxaloacetic transaminase and alkaline phosphatase. KMBC is the second established cell line that originated from a human extrahepatic bile duct carcinoma in the world literature, and it will be applicable to various experiments.
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PMID:Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC). 131 90

A prospective study of 113 patients with jaundice and 20 patients with unjaundiced cholestasis was carried out to evaluate the value of serum tumour markers, carcinoembryonic antigen (CEA) and monoclonal antibodies CA 50 and CA 242, in the distinction between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 37) the serum values of all tumour markers were significantly higher than in the patients with benign disease (n = 96). The sensitivities of CEA, CA 50 and CA 242 in detecting malignancy were 70.2%, 94.5% and 56.7%, respectively, while the specificities were 57.2%, 33.3% and 77.0%, respectively. Serum alkaline phosphatase and bilirubin levels had a high positive correlation with CA 50, and CA 242 correlated positively with serum bilirubin levels. No correlation was seen between CEA and alkaline phosphatase or bilirubin levels. The CEA, CA 50 and CA 242 tests may be used as useful complements to other investigative methods in the distinction between benign and malignant causes of jaundice and/or cholestasis. In particular, the rather high specificity of the CA 242 test for malignant diseases seems promising.
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PMID:Clinical value of serum tumour markers CEA, CA 50 and CA 242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis; results from a prospective study. 133 81

We have established a cell line (KU-SN) from a peripheral neuroectodermal tumor originating in the left scapula of a 4-year-old girl. The original tumor was immunoreactive with antibodies for neurofilament proteins, neuron-specific enolase, vimentin, S100 protein, and beta 2-microglobulin. Dense core granules, 50-150 nm in diameter, were identified by electron microscopy. The cell line was established from tumor cells in metastatic lung fluid. KU-SN cells were immunoreactive with the antibodies for neurofilament proteins, vimentin, neuron-specific enolase, S100 protein, glial fibrillary acidic protein, cytokeratin, and carcinoembryonic antigen. Besides these neuronal features, KU-SN cells express type 2 collagen and insulin-like growth factor 1 receptor. The addition of insulin-like growth factor 1 (100 ng/ml) increased the growth rate of KU-SN cells 2.1-fold over control. Some cells were positive for Alcian blue and alkaline phosphatase staining. Cytogenetic analysis of KU-SN cells disclosed a reciprocal chromosomal translocation [t(11,22)]. Northern blot analysis of KU-SN cells demonstrated amplified expression of the c-myc gene but not the N-myc gene. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue. Chondrocytic differentiation was not observed in xenografts of Ewing's sarcoma cell lines SK-ES or RD-ES or the peripheral neuroectodermal tumor cell line SK-N-MC. These results indicate that KU-SN cells represent primitive neural crest cells having the potential for chondrocytic differentiation.
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PMID:Chondrocytic differentiation of peripheral neuroectodermal tumor cell line in nude mouse xenograft. 137 22

HT-29 Human colonic adenocarcinoma cells when grown on a plastic substratum were anaplastic in appearance and failed to express any morphological or biochemical features that were characteristic of intestinal differentiation. Growth of HT-29 cells subcutaneously in the flank of immune deprived mice gave rise to morphologically heterogeneous tumors which were poorly differentiated but contained approximately 11% of cells with an intestinal phenotype: these showed features typical of cell polarization with well-developed microvilli, tight junctional complexes and desmosomes between adjacent cells. The transfer of cells from plastic onto either a fixed (designated 'non-released') or floating (designated 'released') type I collagen gel induced some morphological features typical of intestinal differentiation; for example goblet-like cells were observed after 9 days, but biochemical markers of differentiation were expressed only modestly. The continued subculture of HT-29 cells on collagen type I gels, which were either attached to the plastic or floating in the medium, induced some morphological features of intestinal differentiation and changes in the activity of brush border-associated enzymes. Alkaline phosphatase activity was enhanced from 1.3 x 10(-3) mumoles/mg/min for cells cultured on plastic substrata to 2.1 x 10(-3) mumoles/mg/min when gels were non-released, and 2.9 x 10(-3) mumoles/mg/min when gels were released after 12 days of culture. This was confirmed by electron microscopical visualization of alkaline phosphatase activity. Elevated levels of aminopeptidase activity were also observed on day 12 (plastic = 26 milliunits/mg; non-released gel = 41 milliunits/mg; released gel = 36 milliunits/mg). Similarly, changes occurred in the secretion of carcinoembryonic antigen from 0.96 x 10(-2) micrograms/mg/48 hours by cells cultured on plastic to 2.3 x 10(-2) micrograms/mg/48 hours by cells cultured on floating collagen gels. The effects of permitting HT-29 cells to undergo polarization were tested by culture on inert filter inserts: morphological features of intestinal differentiation were observed although this did not occur until after 21 days. These studies show that optimization of the growth conditions of anaplastic cells in vitro may provide cultures more representative of the tumor in vivo. This model system may be useful for cell biological and pharmacological studies of colon carcinoma.
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PMID:The influence of type I collagen on the growth and differentiation of the human colonic adenocarcinoma cell line HT-29 in vitro. 142 2

The selective targeting of tumors by enzymes conjugated to monoclonal antibodies (mAb) may be an ideal approach to convert relatively nontoxic prodrugs into active agents at the tumour site. We used the anti-carcinoembryonic antigen mAb BW431/26 conjugated to alkaline phosphatase (AP) and phosphorylated etoposide (etoposide-P) as a prodrug to study the feasibility of this concept. Etoposide was phosphorylated with POCl3. Quantitative hydrolysis of etoposide-P to etoposide occurred within 10 min in the presence of AP. BW431/26 and AP were conjugated using a thioether bond. The AP conjugate retained 93% of its calculated activity. 125I-labelled AP conjugate did not show a reduction of immunoreactivity as determined by a cell-binding assay. SW1398 colon cancer cells were used to analyse the cytotoxicity of etoposide and etoposide-P. Etoposide (IC50 22 microM) was 100 times more toxic than etoposide-P (20% growth inhibition at 200 microM). Pretreatment of the cells with BW431/26-AP prior to etoposide-P exposure resulted in a dramatic increase in cytotoxicity (IC50 70 microM). The pharmacokinetics and tumour-localizing properties of BW431/27 and the AP conjugate were assessed in nude mice bearing SW1398 tumours. BW431/26 showed excellent tumour localization (10% of the injected dose/g tissue retained from 8 h to 120 h), whereas the AP conjugate showed a reduced tumour uptake (3%-0.3% of the injected dose/g tissue at 8-120 h), a faster clearance from the circulation and a high liver uptake. Radiolabelled AP showed a similar pharmacokinetic profile to the AP conjugate. Gel filtration analysis of blood, liver, and tumour samples indicated good stability of the conjugate.
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PMID:Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline phosphatase for specific activation of the prodrug etoposide phosphate. 154 Sep 81


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