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

Ovarian carcinoma contains an antigen (TA) which is stable at 100 degrees. Rabbit antisera to glycoprotein-rich extracts of tumors detect TA in 70 per cent of ovarian malignancies, in some benign ovarian cysts, certain normal lung preparations, normal cervix, and squamous-cell carcinoma of the cervix. Highest levels may be associated with mucin secretion. No detectible antigen was present in normal ovary, plasma, A, B, and O erythrocytes, leukocytes, placenta, brain, heart, liver, corpus uteri, spleen, skeletal muscle, or kidney. Prolonged digestion of boiled tumor extracts with papain, trypsin, chymotrypsin, on Sephadex G-150 corresponding to a globular protein of 27,000 to 36,000 molecular weight. A beta-globulin mobility is seen in immunoelectrophoresis. It appears that TA differs in tissue specificity and molecular size from other known ovarian cancer associated antigens.
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PMID:A thermostable antigen associated with ovarian cancer. 6 15

Synthetic glycosides containing the core, -Glc-NAc beta 1,6GalNAc alpha-, acted as acceptors for beta-galactosyltransferase of human ovarian tumor. A significant amount of Gal was transferred from UDP-Gal (100 nmol) to the alpha-benzylglycoside of LacNAc beta 1,6GalNAc (LGBn) (25.1 nmol of Gal) and the alpha-ortho-nitrophenylglycosides of LacNAc beta 1,6GalNAc (22.0 nmol of Gal), GlcNAc beta 1,6GalNAc (15.5 nmol of Gal), and Fuc alpha 1,3GlcNAc beta 1,6GalNAc (25.9 nmol of Gal); LacNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn (where Bn is benzyl) was almost inactive (only 1.2 nmol of Gal), indicating the Gal transfer to the alpha-GalNAc moiety. The product from LGBn was isolated in microgram quantities and identified by fast atom bombardment mass spectrometry as LacNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn. The alpha GalNAc:beta 1,3Gal transferase was present in high concentration in ovarian tumor tissue (ovarian cancer serum----1.4; ascitic fluid----0.9; tumor----17.4). Asialo Cowper's gland mucin (ACGM) at 5 mg/ml reaction mixture inhibited the transfer of Gal to LGBn (25.2 and 53.4% respectively for 2 and 18 h incubation at 37 degrees C); inhibition by LGBn was 13.4 and 24.5%, respectively. In contrast to the inhibition by ACGM (25.2-31.6%), there was substantial increase (13.4-35.7%) in the inhibition by LGBn, when the incubation for 2 h at 37 degrees C was continued for 40 h at 4 degrees C, indicating the high affinity of LGBn for the enzyme at lower temp. Km for LGBn in presence of ACGM was 7.6 mM and in absence, 2.7 mM; Km for ACGM (M(r) 200,000) in presence of LGBn was 16.1 microM and Ki for ACGM (as the inhibitor) was 41.7 microM. In comparison with two normal ovarian tissues, the enzyme was found to be low (55-67%) in three ovarian tumors and high (146-260%) in two ovarian and one uterus tumors, as measured with ACGM; the synthetic acceptors showed similar activities. The enzyme had nearly the same extent of activity in the pH range 6-8. Fuc alpha 1,3GlcNAc beta 1,6GalNAc alpha-O-ONP had the highest affinity for the enzyme. The present study demonstrates the feasibility of beta 1,3Gal attachment on alpha GalNAc, which has already been substituted by beta 1,6GlcNAc, then elongated by beta 1,4Gal and also terminated by alpha 1,3Fuc.
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PMID:Mucin biosynthesis revisited. The enzymatic transfer of Gal in beta 1,3 linkage to the GalNAc moiety of the core structure R1-GlcNAc beta 1,6GalNAc alpha-O-R2. 140 Mar 9

Monoclonal antibodies (moABs) MA54 and MA61, directed toward the O-linked mucin-type glycoprotein, have been established and showed highly specific reactivity with human ovarian cancer. Fetal intestinal and colonic mucosal cells expressed this antigen and meconium staining was also frequently positive. To investigate the characteristic of an epitopic carbohydrate recognized by these moABs, the reactivity of each moAB with meconium extract was monitored by solid-phase enzyme-linked immunosorbent assay with mono-, di-, and oligosaccharides. MA54 and MA61 react with meconium extract and the reactivities of these moABs are neuraminidase sensitive. Ovine submaxillary mucin had a strong inhibitory activity toward the reaction between meconium extract and MA54 as well as MA61, suggesting that these moABs recognize NeuAc 2-6GalNAc epitope in meconium. The second aim of this study is to investigate the possible application of moABs to diagnose ovarian cancer and to compare these levels with those of the CA125 antigen. While serum CA54/61 antigen levels were elevated in 44.4% of ovarian cancer cases and serum CA125 antigen levels were elevated in 86.7% of the same population, the use of both assays indicated a sensitivity of detection of 97.8% (44 of 45 patients) in the population studied.
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PMID:Characterization and clinical evaluation of tumor-associated antigen CA54/61 identified by monoclonal antibodies MA54 and MA61 in epithelial ovarian cancer. 147 46

In the search for a method to facilitate the preoperative discrimination of ovarian carcinomas from colorectal carcinomas serum levels of 6 tumor markers were measured in 47 patients presenting with ovarian cancer and compared to levels found in 24 female patients with advanced, untreated colorectal cancer. The markers studied were CA 125, CA 15.3, CA 19.9, CEA and two recently developed mucin markers, CA M29 and CA M26. Levels of CA 125, CA 15.3, CEA and CA M29 showed significant differences between both groups. In predicting ovarian cancer, sensitivity was highest for CA 125 at 94% (35 U/ml cutoff level). However, the specificity of CA 125 was at 71% low. Specificity increased significantly by using a combination of a CA 125-positive score (greater than 35 U/ml) and a simultaneous negative CEA score (less than or equal to 5 ng/ml) (specificity 100%, sensitivity 81%). A CA 125/CEA serum ratio greater than 25 resulted in the highest discriminative power with a specificity of 100% and a sensitivity of 91% resulting in an overall test accuracy of 94%. It is concluded that the serum tumor markers used, especially a combination of CA 125 and CEA, are helpful in the preoperative differential diagnosis between adenocarcinomas of ovarian and colorectal origin.
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PMID:Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas. 158 94

Because a highly sensitive and specific serum marker for ovarian carcinoma has not been reported, it is unlikely that there will be an application of serum markers for screening for this disease in asymptomatic women. However, many oncologists use serum tumor markers initially to differentiate epithelial ovarian carcinoma from benign gynecological conditions prior to surgery, so as to ensure appropriate surgical referral, and then to monitor the clinical course of disease during and after adjuvant therapy. The most commonly performed tumor marker assay in ovarian cancer (CA125) has been extremely valuable in patient management, but this marker is also elevated in a considerable proportion of patients with benign gynecologic diseases and endometriosis, and a relatively small proportion of patients with early stage disease. A new class of serum tumor markers, the highly glycosylated, high molecular weight mucins, have enormous potential in the management of ovarian cancer patients, since the use of assays for these markers may overcome many of the problems associated with CA125. Indeed, when used in combination with CA125, some mucin-based assays have increased the sensitivity and specificity of detection, thereby eliminating many false positive results seen with patients with benign disease and endometriosis, and also predicted disease recurrence in the majority of patients before clinical symptoms became apparent. These markers are the subject of this review, with particular attention to the commercially-available mucin-based assays.
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PMID:Circulating mucins as tumor markers in ovarian cancer (review). 162 28

Monoclonal antibody (MAb) B72.3 has been shown to be of potential utility in the management of human carcinoma via its use in (a) the targeting of carcinoma lesions in colorectal and ovarian cancer patients, (b) immunohistochemical analyses of biopsies and effusions, and (c) serum assays to help define the presence of carcinoma. The B72.3-reactive antigen, designated tumor-associated glycoprotein 72 (TAG-72), has been characterized as a high molecular weight glycoprotein with the properties of a mucin. We report here the utilization of MAb B72.3 and 18 second generation MAbs (generated using purified TAG-72 obtained from a colon carcinoma xenograft as immunogen) to construct a serological map of the TAG-72 molecule. The generation and initial characterization of 10 of the second generation MAbs have been described previously; in addition, eight previously unreported MAbs were used. All 19 MAbs produced immune precipitate lines against purified TAG-72 in double immunodiffusion, indicating that each epitope recognized by a single MAb is present at least twice on the TAG-72 molecule. Immunodepletion analyses utilizing 11 of the anti-TAG-72 MAbs indicated that each recognizes the same molecule or population of molecules. Nineteen competition radioimmunoassays were developed and 19 purified competitor immunoglobulins were used in each assay. The patterns of cross-competition indicated the presence of a complex array of tumor-associated epitopes on the TAG-72 molecule. Some of the MAbs recognized epitopes that were structurally or spatially related to one another, but none appeared to recognize identical epitopes. The spectrum of inhibitory reactivities of these MAbs for TAG-72 binding varied from extremely restricted to more broad inhibition. The serological mapping studies reported here provide information as to the range and nature of the epitopes expressed on the TAG-72 molecule, help form the basis for selecting alternative anti-TAG-72 MAbs for use in potential clinical applications, and further define the nature of this oncofetal antigen.
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PMID:Serological mapping of the TAG-72 tumor-associated antigen using 19 distinct monoclonal antibodies. 169 62

The monoclonal antibody (Mab) OM-1, which defines the ovarian carcinoma-associated sebaceous gland antigen (SGA), and Mab F36/22, which defines the ductal carcinoma antigen (DCA), were tested for reactivity against a synthetic peptide representing the repeat twenty amino acid sequence of the human polymorphic epithelial mucin core protein plus four amino acids of the adjacent sequence (p1-24). OM-1 bound strongly to the peptide by direct dot blot assay and ELISA and the minimum epitope for OM-1 was shown to be APDTRP(A) by inhibition assay. F36/22 reacted weakly with the peptide under the same conditions and its affinity for peptide in solution was relatively very low. Mab OC125, which defines the ovarian cancer-associated antigen CA125, did not react with the p1-24 peptide. Five other anti-mucin Mabs (HMFG1, HMFG2, BC1, BC2, BC3), previously shown to bind to the p1-24 peptide, reacted strongly with SGA by direct binding and in a sandwich assay with OM-1 as the capture Mab. F36/22 was weakly positive under the same conditions suggesting that both peptide and SGA do not express the optimal epitope for F36/22 binding. These results indicate that SGA and possibly DCA have the repeat sequence core protein of the breast carcinoma-associated human polymorphic epithelial mucin.
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PMID:Monoclonal antibodies reactive with the breast carcinoma-associated mucin core protein repeat sequence peptide also recognise the ovarian carcinoma-associated sebaceous gland antigen. 169 26

We have investigated the action of recombinant human gamma-interferon (rHuIFN-gamma) against human ovarian cancer xenografts growing as ascites or as bulky solid i.p. tumors in nude mice. Both forms of the disease responded to i.p. rHuIFN-gamma with significant increases in mouse survival time, and in 2 of 3 ascitic models the mice were cured of peritoneal disease. The activity of rHuIFN-gamma was dose and schedule dependent, and xenografts derived from 3 different patients showed a heterogeneity of response. Peak i.p. levels of rHuIFN-gamma in nude mice bearing multiple i.p. solid tumors were similar to those found in ovarian cancer patients receiving i.p. rHuIFN-gamma, but clearance was more rapid in the mice. Rat gamma-interferon had no antitumor activity at the same doses and schedules although it had some biological activity in the nude mice. Histological examination of treated tumors revealed increased necrosis and loss of cellular organization with large areas of hypocellular epithelial mucin. These changes were preceded by a fall in tumor tryptophan and a rise in tumor kynurenine. We conclude that rHuIFN-gamma has a direct dose related antitumor effect on ovarian cancer xenografts that is preceded by increased metabolism of tryptophan.
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PMID:Antitumor activity of gamma-interferon in ascitic and solid tumor models of human ovarian cancer. 174 38

Sialyl Tn antigen (NeuAc alpha 2----6GalNac alpha 1----0-Ser/Thr [STN]) with antigenic specificity in the core structure of mucin-type carbohydrate chains has been determined. In the present study, we evaluated the clinical significance of this new carbohydrate antigen, STN, in patients with epithelial ovarian cancer. With the use of a radioimmunoassay developed to detect STN antigen in serum, elevated (greater than or equal to 32.6 U/mL) antigen levels were observed in 50.0% of patients with ovarian cancer. In contrast, 3.8% of healthy individuals had STN antigen levels greater than or equal to 32.6 U/mL. In 9.6% of patients with benign gynecologic diseases and 0% of pregnant women, there were elevated levels of STN antigen. There was a significant difference (P less than .001) in STN antigen levels between patients with ovarian cancer and patients with benign gynecologic diseases, pregnant women, or the controls. The mean +/- SD for all evaluated samples of ovarian cancer was 109.2 +/- 146.8 U/mL. Both the mean values and the positive rate increased as the stage advanced. Classified according to the histologic type, the highest positive rate (61.0%) was observed in mucinous adenocarcinoma. The usefulness of STN antigen as a circulating tumor marker in ovarian cancer was estimated as follows: sensitivity 50.0%, specificity 93.5%, positive predictive value 72.2%, negative predictive value 84.7%, and diagnostic value 46.8%. Serum STN antigen levels were elevated in 12 of 33 patients with ovarian cancer who had serum CA 125 antigen levels less than 35 U/mL. While CA 125 antigen levels were elevated in 74.6% and STN antigen levels were elevated in 50.0% of the same population, the use of both assays indicated the sensitivity of detection of 83.8% in the population studied.
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PMID:Clinical evaluation of circulating serum sialyl Tn antigen levels in patients with epithelial ovarian cancer. 185 22

Two recently developed monoclonal antibody (MAb)-based anti-mucin assays, CA M26 and CA M29, were studied in 250 cancer patients and compared to 3 well-established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their clinical usefulness as serum tumor markers. Pre-treatment sera were obtained from patients with predominantly low-stage epithelial malignancies comprising 200 adenocarcinomas (of the ovary, endometrium, breast and large intestine) and 50 squamous-cell carcinomas (of the uterine cervix). Pretreatment sera of 50 patients with benign ovarian tumors were included to evaluate levels in benign disease, CA M26 and CA M29 cut-off levels were established in 89 healthy controls. In patients with adenocarcinomas, overall positivity for CA M29 was 24%, ranging from 10% in breast cancer to 60% in ovarian cancer. Overall positivity was highest for CA 125 (30%) and lowest for CA M26 (18%) with CA M29 (24%) being similar to CA 15.3 (25%). In adenocarcinomas the combined CA M26-CA M29 assays equalled results obtained with the CA 125-CA 15.3 combination (33% vs. 36%). Elevation of 2 or more markers was highly indicative of advanced disease (p less than 0.025). A majority of positive patients showed either CA M26 or CA M29 elevations, indicating that both antibodies detect distinct epitopes. After adjustment for tumor site and stage, the profile of CA M26 as a single marker differed significantly from the profiles of CA 125 and of CA M29. CA M26 was frequently (32%) elevated in patients with squamous-cell carcinoma of the cervix and CA M26 levels were often independently elevated. CA M26 seems to be valuable as an additional marker in breast cancer and perhaps as a new marker in cervical cancer. CA M29 may be useful in ovarian cancer in addition to CA 125.
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PMID:Carcinoma-associated mucin serum markers CA M26 and CA M29: efficacy in detecting and monitoring patients with cancer of the breast, colon, ovary, endometrium and cervix. 198 62


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