Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibition of normal human placental alkaline phosphatase, its rare "D-variant" phenotype, and the "Nagao isoenzyme" found in an ovarian cancer fluid by peptides containing L-leucine were studied. The Nagao isoenzyme and the D-variant phenotype were distinct from the normal placental enzyme, but similar to each other in their inhibition by L-leucine and dipeptides containing L-leucine in their amino termini. On the other hand, L-leucinamide, L-Leu-L-Leu-L-Leu and L-Leu-Gly-Gly inhibitions did not readily discriminate between D-variant and normal phenotypes, but did so between D-variant and Nagao isoenzymes. The distinctions among these enzymes in their responses to peptide inhibitors may reflect differences in their primary structures.
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PMID:Inhibition of human placental-type alkaline phosphatase variants by peptides containing L-leucine. 85 96

A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed chromosomal alterations. One of the marker chromosomes showed characteristics of a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation using specific probes to the Y chromosome. The cells stained with fluorescent antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin but not with desmin. The presence of epithelial membrane antigen, human milk fat globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase and oestrogen receptor-related antigen was demonstrated by indirect immunoperoxidase staining, but no CA-125 antigen could be detected. The cells showed positive reaction with antibodies to P-glycoprotein. The function of the P-glycoprotein transport system was demonstrated by the rhodamine-123 release test. The cells were initially responsive to doxorubicin, and to high concentrations of cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced by the addition of verapamil or tamoxifen. This was shown by the soft agar clonogenic assay, by direct cell counting and by the MTT reducing test. Our results show that combination between drug and sensitivity modulators may be of potential clinical value in ovarian cancer.
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PMID:A cell line with unusual characteristics from an ovarian carcinoma patient: modulation of sensitivity to antitumour drugs. 134 52

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.
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PMID:Coordinate elevation of serum markers in ovarian cancer but not in benign disease. 191 20

Pretreatment serum levels of the antigens CA-125, tissue polypeptide Antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were determined in samples from 295 women with adnexal masses. At laparotomy 48% of patients had epithelial ovarian carcinoma, 9% had tumors of low malignant potential, and 8% suffered from malignancies of other kinds. The sensitivity of CA-125 with 35 U/ml as the cutoff was 88% in women with ovarian carcinoma, but 74% among those with limited disease and 58% in borderline malignancy. Only 6 of 17 mucinous ovarian carcinomas were detected. Specificity was 83%. CEA was elevated above 5.0 micrograms/liter in 15 of 17 patients with mucinous ovarian cancer. TPA detected advanced stages of malignancy, but the sensitivity was low, 53%, in cases with limited disease. PLAP was elevated in 46% of ovarian carcinoma patients. For detecting malignancy overall, the use of a parallel combination of the CA-125 and CEA assays was more sensitive than use of CA-125 as a single marker. This test combination may be of value in the diagnosis of adnexal masses. The predictive value of a positive result was 90%, and that of a negative result, 76%.
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PMID:Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase, in patients with ovarian carcinoma, borderline tumors, or benign adnexal masses: relevance for differential diagnosis. 222 69

A permanent human neoplastic cell line, DO-s, was established from ascites of a patient with a well-differentiated mucinous cyst-adenocarcinoma of the ovary. This cell line grew as vermiform, floating colonies of epithelial cells in culture. The karyotype of DO-s was of a human female; the chromosome number ranged from 54 to 66 with several abnormalities, mainly trisomy. Epithelial-like character was confirmed by transmission electron microscopy and by the presence of cytokeratin. Inoculation of DO-s cells i.p. or s.c. in athymic nude mice resulted in, respectively, ascites and xenografts. Light and electron microscopical analysis of cultured cells and xenografts demonstrated that the cell line was derived of a mucinous adenocarcinoma biopsy. Tumor-associated antigens, cancer antigen 125 (CA 125), human milk fat globulin, and human placental alkaline phosphatase were expressed by cells in culture and in xenografts. Modulation of the antigens, CA 125 and human milk fat globulin, occurred in DO-s cells growing in athymic mice. Biochemical, immunohistochemical, and histochemical analysis showed that more than 50% of the alkaline phosphatase isoenzymes present in DO-s cells had the characteristics of human placental alkaline phosphatase and placental alkaline phosphatase-like alkaline phosphatase (AP), but fractions of intestinal AP and nonspecific AP (bone-liver-kidney) were also present. The expression of AP isoenzymes could be induced by an enhancement of the serum supplement in the culture media, and by dexamethasone, sodium butyrate, and bromodeoxyuridine. This line will be a valuable tool in studying the therapeutic effects of antibodies to tumor-associated antigens or other agents for ovarian cancer.
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PMID:Establishment and characterization of a human ovarian neoplastic cell line, DO-s. 254 14

A specific radioimmunoassay for human placental alkaline phosphatase has been developed using the 125I-labeled enzyme, highly purified with a fast protein liquid chromatography system and an absorbed rabbit antiserum. The sensitivity of this assay was 0.2 U/L. Serum levels of over 0.2 U/L were found in 27% of ovarian cancer patients, and most of these elevated enzyme levels occurred with more advanced stages of the disease. On the other hand, almost all ovarian cancer tissue contained detectable levels of the enzyme. Serous adenocarcinoma, endometrioid adenocarcinoma, and dysgerminoma had particularly large amounts. Placental alkaline phosphatase was more frequently detected in tissue than in the serum of ovarian cancer, and therefore may be a useful target in immunodetection and immunotherapy and in studying the histopathology of ovarian cancer.
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PMID:Radioimmunoassay of placental alkaline phosphatase in ovarian cancer sera and tissues. 302 85

Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with ovarian cancer, 79 patients with testicular cancer (53 seminoma testis, 26 nonseminoma testis), 537 patients with various other malignant diseases (95 lung, 39 gastrointestinal, 195 breast, 208 others), 291 patients with benign diseases, and 213 healthy controls. To assess the influence of smoking on hPLAP activity in serum, we evaluated 79 serum samples from patients with noncancerous diseases for whom smoking habits had been recorded. Our main findings are: (a) hPLAP activity is frequently increased (greater than 100 mU/L) in pre-operative serum samples from ovarian cancer patients (49%) and from testicular cancer patients (59% overall; 72% seminoma, 35% nonseminoma); (b) heavy smoking may increase hPLAP activity; (c) excluding heavy smokers, a 96% specificity for cancerous lesions was observed; (d) in patients with ovarian malignancies, CA 125 and hPLAP may behave as independent markers; and (e) in patients with seminoma, hPLAP is clearly more frequently increased than is beta-choriogonadotropin.
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PMID:Multicenter evaluation of human placental alkaline phosphatase as a possible tumor-associated antigen in serum. 316 10

In 1930 the determination of serum alkaline phosphatase in patients with bone or liver disease ushered in the era of clinical enzymology. The association of elevated (bone) alkaline phosphatase in serum of patients with osteogenic sarcoma was the first evidence that tumor cells themselves produced the enzyme. It became clear, however, in the 1960s that the serum alkaline phosphatase was not a single enzyme but consisted of a family of isozymes originating from liver, bone, intestine, and placenta. This was a consequence of the introduction of a combination of electrophoretic separations, heat inactivation, and organ-specific amino acid inhibitors. This combination of measurements made possible the demonstration of a serum alkaline phosphatase of lung cancer origin, as confirmed by the histochemical visualization in lung cancer of the Regan Isozyme (placental alkaline phosphatase-PLAP). At present, the measurement of PLAP has its greatest utility as a tumor marker in seminoma and ovarian cancer. A PLAP-like isozyme in normal testis and ovary is expressed in these and other neoplasias and appears to be related to rare alleles of placental alkaline phosphatase. Current studies have utilized a panel of monoclonal antibodies to detect useful epitopes that suggest that PLAP and PLAP-like isozymes are coded by different genes. The PLAP gene has now been cloned and sequenced by Millan and others. This fundamental new information is providing a base line that will make it possible to explain the overlapping specificities of intestinal and placental isozymes, the degree of uniqueness of the PLAP-like isozyme, the precise mechanism of uncompetitive inhibition by L-phenylalanine and the evolutionary history of the alkaline phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and biological significance of an isozyme tumor marker--PLAP. 332 92

The serum concentrations of CA 125 and placental alkaline phosphatase were analyzed in 16 patients with ovarian cancer. Increased serum levels of CA 125 and placental alkaline phosphatase were observed in 75% and 50% of the cancer patients, respectively. The serum levels of these tumor markers were not correlated, supporting their distinct antigenic nature. CA 125 seems to be a more promising tumor marker for ovarian cancer than placental alkaline phosphatase.
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PMID:Comparison of CA 125 and placental alkaline phosphatase as ovarian tumor markers. 347 19

Using continuous human ovarian cancer cell lines, i.p. xenografts were successfully established in nude mice from four of four attempts. When primary tumor material was used, xenografts grew in 8 of 10 attempts. From these eight, three passageable xenograft cell lines have been established. To our knowledge, this is the first report published of such xenografts. I.p. xenografts closely mimic the clinical behavior of human ovarian cancer, and those developed from primary tumor material maintain close morphological similarity to the parent primary tumor. When expression of placental alkaline phosphatase and the tumor associated antigens defined by the monoclonal antibodies HMFG1, HMFG2, AUA1, and F36/22 by these models was determined, those i.p. xenografts derived from primary tumor material exactly matched the original tumor, while none of the xenografts derived from the cell lines expressed these antigens. These models will be useful for investigating the biology and treatment of ovarian cancer.
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PMID:Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. 356 97


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